Transcript (+) Gastric juice

Gastrointestinal physiology
Yue Limin(岳利民)
Department of Physiology
School of Preclinical and Forensic Medicine
Sichuan University
The old saying
"you are what you eat"
"you are what you absorb and digest".
Introduction
Concepts of digestion and absorption
Characteristics of the smooth muscle of
gastrointestinal tract
Secretory function of digestive gland
Neural control of gastrointestinal tract
Endocrine function of gastrointestinal tract
Ⅰ. Concepts of digestion and absorption
The main types of foods
Carbohydrads, fat , protein
large molecules
Vitamine, inorganic salt, water
fiber
small
molecules
Digestion:
The breakdown of proteins, fats and carbohydrates
into absorbable molecules in the gastrointestinal tract.
Protein
amino acid
Carbohydrate
Fat
monosaccharide
fatty acid and glycerol
Absorption:
The movement of the digested products ,water and
electrolytes from the lumen of digestive tract into the
lymph or the blood.
closed relationship between digestion and absorption
How are the foodstuffs digested ?
Mechanical Digestion:
The motility of smooth muscle in gastrointestinal
tract grinds food and mixes it with digestive
juice to prepare it for chemical digestion and
absorption, and then propels the food
along the gastrointestinal tract.
Chemical Digestion:
Nutrients in the food are broken down by the
enzymes in digestive juice secreted by the
secretory glands.
Ⅱ.Characteristics of Gastrointestinal
Smooth Muscle
1. General physiological characteristics
low
excitibility
slow
contractility
high
extensibility
tonicity
Sensitive
for chemical, thermal and
mechanical stretch stimulation
2. Electrophysiological characteristics
Resting potential
Slow wave potential
Action potential
Resting potential of smooth muscle IN GI
Value: -50
-60mV
Formation:
out flow of K+ ; Na+ Ca2+
electrogenic Na+ -K+ pump
Slow wave or basic electric rhythm (BER)
Definition: Spontaneous, slow and rhythmic
fluctuation ( depolarization and repolarization)
on resting potential in gastrointestinal smooth
muscle cells.
Size: 5-15mV (from –65 to-45mV)
Frequency: 3-12/min
stomach--- 3; duodenum---12; ileum---8，9
Size and frequency is influenced by neural and
humoral regulation.
Origin: interstitial Cajal cells, which serve as
pacemaker for GI smooth muscle
Mechanism: cyclic changes of the activity of
Na+ -K+ pump
Function: weak contraction
the base of AP formation
Action Potential
Inducing: the depolarization of slow wave
reaches TP by stimulation
Characteristics: single or mutiple spikes
Action: the number of spike potential determine
contraction
Mechanism:
depolarization: slow Ca2+-Na+channels
Ca2+ inward flow , Na+ inward flow
repolarization:
K+ outward flow
Relationship among RP, BER and contraction
frequency
direction
speed
RP
AP
Muscle Contraction
strength
3. Basic types of movements in digestive tract
mastication and swallowing:
Tonic contraction: a constant level of contraction,
without regular period of relaxation
Peristaltic contraction: a series of coordinated sequential
contraction.
Migration motor complex (MMC)
Mass movement
Segmentation contraction: alternate contraction and
relaxation of a section of intestine
Receptive relaxation: stimulation of food on pharynx and
esophagus produce relaxation of the lower esophageal
sphincter and the orad stomach.
Peristalsis
contraction
relaxation
Segmentation
contraction
Ⅲ. Secretory function of digestive glands
Secretion is the addition of fluids, enzymes
and mucus from the digestive glands to the
lumen of gastrointestinal tract.
Main digestive gland:
salivary glands
saliva, 1500 ml/day
gastric gland
gastric juice, 2500 ml/day
exocrine cells of pancreas
pancreatic
juice, 1500 ml/day
liver
bile, 500 ml/day
Main Effects of Digestive Juice
Hydrolyze nutrients into absorbable units
Dilute the food in favor of absorption
Change the pH value in digestive cavity to
meet the need of digestive enzymes
Mucous, antibodies and fluid in digestive
juice protect gastrointestinal mucosa from
physical and chemical injuries
Major digestive enzymes in main digestive juice
Source
saliva
Gastric
juice
enzyme
substrate
a-amylase
starch
pepsin
protein
a-amylase
starch
lipase
triglycerides
Pancretic trypsin
protein
juice
chymotrypsin polypeptides
carboxypolypeptidase
bile
no enzyme
bile salts
products
maltose,dextrin
maltotriose
polypeptide
maltose, dextrin
maltotriose
monoglyceride
fatty acids
polypeptide
amino acid
Carbohydrate (CHO) Digestion
Digestion of Fat
• Emulsification
by bile salts
• Pancreatic
lipase
• Micelles are
water-soluble
colipase
Ⅳ. Neural control of gatrointestinal tract
1. Central Nervous System (CNS)
Positions:
medulla oblongata: maintain basic function of
gastrointestinal tract
hypothalamus: higher nervous center for gastrointestinal
activities. e.g. feeding center, satiety center
limbic cortex in cerebral cortex (hippocampus, amygdala):
control the activities of hypothalamus
2. Extrinsic nervous system
sympathetic innervation
enteric neuron
postganglionic N. smooth muscle
Preganglionic N.
Cholinergic N. ACh adrenergic N. NE endocrine cell
thoracic and celiac ganglion
secretory cell
lumbar spinal superior mesenteric~
Inhibition
cord segments inferior mesenteric~
sphincters+
(T5—L2)
Parasympathetic innervation
Vagus nerve
sphincters-
postganglionic N.ACh excitation
preganglionic N.
cholinergic N.
vessels
cholinergic N. ACh
peptidergic Peptidesrelaxation
motor nucleus
upper parts
of vagual nerve myenteric and
submucosal plexuses
stomach
in medulla
in the wall of gut
small intestine
oblongata
ascending colon
right transverse
colon
Pelvic nerve
postganglionic N.ACh excitation
preganglionic N.
cholinergic N.
cholinergic N. ACh
relaxation
peptidergic
Peptides
sacral spinal
Cord(S2--S4)
myenteric and
submucosal plexuses
in the wall of gut
lower parts
left 1/3
transverse
colon
Salivary
glands
stomach
liver
pancreas
intestine
pelvic nerve
Pelvic N
3. Intrinsic or Enteric Nervous System (ENS)
The nervous networks of neurons and nerve
fibers in the wall of gastrointestinal tract
Components:
myenteric plexus: between the longitudinal
and circular muscle layers
submucosal plexus: between the middle
circular muscle layer and the mucosa
characteristics
local reflexes
being controlled by extrinsic nerves
Spinal cord sympathetic
Brain sterm
parasympathetic
myenteric
plexus
submucosal
plexus
Sensory
neurons
epithelium
conditoned stimuli
eye,nose,ear
ⅠⅡⅧ
Center
Afferent N.
Efferent N.
Long reflex
receptor
muscle
gland
plexus
Short reflex
Unconditioned Stimuli
contraction
secretion
Ⅴ. Endocrine function of gastrointestinal tract
the biggest endocrine organ
more than 40 types of endocrine cells
first discovered hormone – Starling and Bayliss , 1902
HCl
Intestine without
nerve innervation
extract
Mucosa of
duodenum
blood
blood
∥
Secretion of
pancreatic juice
Ernest Starling
William Bayliss
John Henderson: Ernest Starling and ‘Hormones’: an
historical commentary. Journal of Endocrinology
2005，184, 5-10
1. Gastrointestinal Hormones:
biologically active polypeptides secreted by
the endocrine cells in gastrointestinal tract
which influence the motility and secretion of
gastrointestinal tract.
2. Pathways of gastrointestinal hormones secretion
•
•
•
•
•
endocrine
paracrine
neurocrine
autocrine
solinocrine
3. Functions of Gastrointestinal Hormones
Regulating activities of the
gastrointestinal tract
Trophic act ion
Regulating the secretion of other
hormones
Regulating immune function
4. Brain-gut peptide : exists both in CNS and
gastrointestinal tract
more than 20 kinds: gastrin, CCK, Motilin,
neurotensin
Stimulus and Response of a few Gastrointestinal Hormones
hormone
Gastrin
Secretin
CCK
cholecystokinin
GIP
Motilin
secretion
effects
.
Antrum,upper small (+) Gastric juice
intestine
(+) pancreatic enzymes
(+) Gastric motility
G cell
(+) Trophic to mucosa
Upper small
(+) Pancreatic juice HCO一3
intestine
(+) Bile flow
(-) Gastric acid
S cell
Upper small
intestine
I cell
Upper small
intestine
K cell
Mo cell
(+) Pancreatic enzyme
(+) Gallbladder
contraction
(-) gastric juice secretion
(-)motility of stomach
(+) insulin secretion
(+) Gastric and small
intestinal motility
Digestive function of Stomach
Ⅰ. Secretion of Gastric Juice
Gastric juice: the fluid secreted by the cells of the gastric
mucosa
Major exocrine glands in mucosa
mucous gland: mucus
oxyntic gland in the body: 4 cell types
Parietal cells
body
HCl, intrinsic factor
Chief cells
body
pepsinogen
Neck mucous cell antrum
mucus; pepsinogen
G cell
gastrin
antrum
pyloric gland in the antrum: G cell; mucous cell
The components and their functions of gatric juice
1. Hydrochloric acid(gastric acid)
Production: parietal cell
action: pepsinogen HCl pepsin
kill bacteria
secretion of secretin
absorption of Ca2+ and Fe2+
Warren and Marshall discovered Helicobacter
pylori,Hp In 1983, and got Noble prize in 2005
Lumen
Gastric parietal cell
Blood
Na+
ATP
K
+
K+
Proton ATP
pump
HCl is
secreted
H+
HCO3-
H2CO3
Cl-
Carbonic
anhydrase
K+
_
Cl
_
HCO3
alkaline tide
CO2
+
H2O
Cellular mechanism of HCl secretion
2. Pepsinogen:
Production: chief cell and mucous cell
Activation: pepsinogen
HCl
+
Action: Hydrolyze protein
pepsin
3. Mucus:
Production: epithelial cell, mucous neck
cell, pyloric gland
Characteristics: glycoproteins; viscid; gel
Action: to form mucus-bicarbonate barrier
with HCO3- that protects the gastric
epithelium from damage of H+and pepsin
HCl
H+
pH2
Layer of mucus
－
HCO
3
pH7
4. Intrinsic factor:
Production: parietal cell，glycoprotein
Action: the absorption of vitamine B12 in ileum
pernicious anemia
Ⅱ. Regulation of gastric secretion
Substances that stimulate HCl secretion in the body
H+
Ca2+
ACh
M
IP3
cAMP
Ca2+
IP ?
3
Gastrin
H2
Histamine
Cholinergic
neuron
paracrine
endocrine
G cell
EnterochromaffinGastrin
ACh
like cell
Substances that inhibit gastric secretion in the body
somatostatin: Gi
(-)
neurotensin
epidermal growth factor
GIP
secretin
AC
cAMP
Regulation of gastric secretion during the digestive period
Conditoned stimuli
ⅠⅡⅧ
unconditioned Stimuli
Ⅹ
Distension of fundus ,body
GastricDistension of antrum
food phase
Chemical stimuli
ⅤⅦ
ⅨⅩ
plexus
G cell
Ⅹ
Gastric
gland
gastrin
Mecho-chemical stimuli
Entero-oxyntin
cephalic phase: large amount(30%); high acid intensity
large amount of enzyme
gastric phase: large amount(60%); less acid intensity
less amount of enzyme
Ⅲ. Inhibition of gastric secretion during the
digestive period
HCl
negative feedback
In stomach:
inhibit secretion of gastrin from G cell
in the antrum of stomach
stimulate the release of somatostatin
from D cell
In duodenum:
promote release of secretin
release of bulbogastrone
Fat
enterogastrone
Hyper-osmotic fluid
Entero-gastric reflex
one or a few kinds of hormones
Ⅳ. Gastric emptying
Definition: The process that the gastric contents
are delivered to the duodenum.
Driving force: Difference of pressure between
stomach and duodenum
Characteristic: discontinued
Factors influencing gastric emptying:
Physical and chemical characteristics of food
Liquids＞solid;
isotonic＞hypotonic or hypertonic
Carbohydrate＞protein＞fat
Regulation of stomach emptying
Gastric factors that promote emptying:
Stretching and chemical stimuli
local reflexes
vagovagal reflex
gastrin
Duodenal factors that inhibit emptying
Mechanical and chemical stimuli
Entero-gastric reflexes
secretin; gastric inhibitory peptide(GIP)
Cholecystokinin(CCK);
enterogastric reflexes are sensitive to pH,
products of protein digestion and hypertonic fluid
Absorption
The location of absorption:
structure
stomach
bile
digested degree of food
time of food staying
Small intestine is ideally
suited for absorption of
quantities of nutrients
Ca2+
Mg2+
Fe2+
monosaccharides
saccharobiose
Water soluble Vit
panreatic
enzymes
Small
intestine
fat-solubleVit
amino acid
glycerol,fatty acid
Vit B12
bile salt
colon
Absorption in the small intestine
Structural basis:
increse of surface area
surface area
cm2
fold of
kerckring
villi
microvilli
central
lacteal
blood
capiliaries
Two pathes for absorption:
Cellular path: cross the apical(luminal) membrane
enter epithelial cell
extruded from the
cell cross the basolateral membrane
into blood.
Paracellular path: across the tight junction between
intestinal epithelial cells through
intercellular spaces into blood
Basic ways of absorption:
active transport
passive transport
exocytosis and endocytosis
Carbohydrate (CHO) Absorption
Absorption of Fat
• Monoglycerides and long
FA enter cells by diffusion
• Triglyceride synthesis
• Add protein
• Chylomicrons
• To lacteal (lymph)
• Short FA diffuse into
blood
Defecation
The elimination of fecal waste through the anus
A reflex initiated by the stimulation of strech
receptors in the rectum
S2-4
contraction of rectal muscles
relaxation of the internal anal
sphincter
Prarsympathetic N.
Pelvic N.
relaxation of the external anal
sphincter.
Pudendal N.
Pudendal N.
Constipation:
Prolonged distention of the L. intestine.
Too dry feces due to absorption of water.
Causes:
Ignoring the urge.
Reduced intestinal motility.
Obstruction due to (tumor, or spasm).
Impairment of the defecation reflex.
Problems
Explain:
digestion ; absorption; chemical digestion;
mechanical digestion; slow wave or basic electric rhythm
(BER); brain-gut peptide; gastrointestinal hormones
mucus-bicarbonate barrier in stomach
What
is relationship among RP, BER and contraction of
smooth muscle in GIT
What’s
major components and their functions of gastric
juice, saliva; pancreatic juice and bile and describe the
regulation of the secretion of these digestive juices
Describe
the regulation of gastric secretion during the
digestive period and the characteristics of each phase
Why
is small intestine a main location of absorption
What’s
the functions of major gastrointestinal
hormones
Describe
the innervation of gastrointestinal tract
Supposing
you ate a fried egg and a loaf of bread
in your breakfast, please think about how are the
foods digested and the nutrients in the foods absorbed
clinic, some drugs inhibiting the H+ secretion of
stomach are used to treat gastric or duodenal ucler.
Can you design some drugs for this.
In
The
basic process of defecation
Clinical Case
A 36-years –old woman had 75% of her ileum
resected following a perforation caused by severe
Crohn’s disease (chronic inflammatory disease of the
intestine). Her postsurgical management included
monthly injections of vitamin B12. After surgery, she
experienced diarrhea and noted oil droplets in her
stool. Her physician prescribed the drug
colestyramine(消胆胺） to control her diarrhea, but
she continues to have steatorrhea（脂肪便）.
Question: Could you please explain the woman’s
symptoms and why injections of vitamin B12 was
needed after surgery
相关知识：
• 胆汁的主要成分和作用
• 胆盐的肠肝循环
• 胃液中内因子的主要作用及作用机制
参考资料
Textbook of Medical Physiology. Guyton & Hall. 北京医科
大学出版社(影印),2002
医学生理学（从临床导向到基础医学生理学的途径）。秦
晓群等翻译，科学出版社，2005
http://en.wikibooks.org/wiki/Human_Physiology/The_gastrointestinal_system
http://en.wikipedia.org/wiki/Gastrointestinal_physiology
http://www.vivo.colostate.edu/hbooks/pathphys/digestion/basics/index.html
Structure of digestive system
Digestive tract: mouth, esophagus, stomach,
intestine(small, large, rectum ),
anus
Large ~: salivary gland ,liver
pancreas
Digestive glands:
Small ~: gastric glands ,
intestinal glands
Enzyme
Carbohydrate Digestion:
Produced In
Site of Release
pH Level
Salivary amylase
Pancreatic amylase
Maltase
Protein Digestion:
Salivary glands
Pancreas
Small intestine
Mouth
Small intestine
Small intestine
Neutral
Basic
Basic
Pepsin
Trypsin
Peptidases
Nucleic Acid Digestion:
Gastric glands
Pancreas
Small intestine
Stomach
Small intestine
Small intestine
Acidic
Basic
Basic
Nuclease
Nucleosidases
Fat Digestion:
Pancreas
Pancreas
Small intestine
Small intestine
Basic
Basic
Lipase
Pancreas
Small intestine
Basic