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Gastrointestinal Physiology
Yue Limin(岳利民)
Department of Physiology
School of Preclinical and Forensic Medicine
Sichuan University
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
生理学课程网址：http://cc.scu.edu.cn/G2S/Template/View.aspx?course
Id=43&topMenuId=118273&action=view&type=&n
ame=&menuType=1
A old saying"you are what you eat""you are what you absorb and digest".
Introduction
Characteristics of the smooth muscle of
gastrointestinal tract
Neural control of gastrointestinal tract
Secretory function of digestive gland
Endocrine function of gastrointestinal tract
Concepts of digestion and absorption
Ⅰ. Concepts of digestion and absorption
The main types of foods
Carbohydrads, fat , protein large molecules
Vitamine, inorganic salt, water small
molecules
fiber
Digestion:
The breakdown of proteins, fats and carbohydrates
into absorbable molecules in the gastrointestinal tract.
Absorption:
The movement of the digested products ,water and
electrolytes from the lumen of digestive tract into the
lymph or the blood.
Protein amino acid
Carbohydrate monosaccharide
Fat fatty acid and glycerol
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.
1. General physiological characteristics
Ⅱ.Characteristics of Gastrointestinal
Smooth Muscle
➢low excitibility and slow contraction
➢high extensibility
➢tonicity
➢Sensitive for chemical, thermal and mechanical stretch stimulation
➢autorhythmicity
2. Electrophysiological characteristics
Slow wave potential
Action potential
Resting potential
机械阈电阈
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)
Size: 5-15mV (from –65 to-45mV)
Definition: Spontaneous, slow and rhythmic
fluctuation ( depolarization and repolarization)
on resting potential in gastrointestinal smooth
muscle cells.
Frequency: 3-12/min
stomach--- 3; duodenum---12; ileum---8，9
Size and frequency is influenced by neural and
humoral regulation.
Function: weak contraction
the base of AP formation
Mechanism: cyclic changes of the activity of
Na+ -K+ pump
Origin: interstitial Cajal cells, which serve as
pacemaker for GI smooth muscle
mechanical threshold
Action Potential
Inducing: the depolarization of slow wave
reaches TP（electrical threshold）
by stimulation
Characteristics: 10-20ms, 60-70mV
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
AP Muscle ContractionRP
frequencydirectionspeed
strength
3. Basic types of movements in digestive tractmastication
swallowing:
Oral phase: voluntary movement
Pharyngeal phase: reflex
Esophageal phase
Peristaltic contraction: a series of coordinated sequential
contraction.
Tonic contraction: a constant level of contraction,
without regular period of relaxation
Segmentation contraction: alternate contraction and
relaxation of a section of intestine
Migration motor complex (MMC)
Mass movement
Receptive relaxation: stimulation of food on pharynx and
esophagus produce relaxation of the lower esophageal
sphincter and the orad stomach.
Ⅲ. Secretory function of digestive glands
Main digestive gland:
Secretion is the addition of fluids, enzymes
and mucus from the digestive glands to the
lumen of gastrointestinal tract.
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
Dilute the food in favor of absorption
Change the pH value in digestive cavity to
meet the need of digestive enzymes
Hydrolyze nutrients into absorbable units
Mucous, antibodies and fluid in digestive
juice protect gastrointestinal mucosa from
physical and chemical injuries
Major digestive enzymes in main digestive juice
Source enzyme substrate products
saliva a-amylase starch maltose,dextrin
maltotriose
Gastric
juice
pepsin protein polypeptide
Pancreticjuice
a-amylase
lipase
starchmaltose, dextrinmaltotriose
triglycerides monoglyceridefatty acids
trypsin
chymotrypsincarboxypolypeptidase
polypeptide
amino acid
proteinpolypeptides
bile no enzyme
bile salts
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)
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
Positions:
2. Extrinsic nervous system
sympathetic innervation
celiac ganglionsuperior mesenteric~ inferior mesenteric~
ACh NE
postganglionic N.
adrenergic N.
thoracic andlumbar spinal cord segments
(T5—L2)
Preganglionic N.
Cholinergic N.
enteric neuron
smooth muscle
endocrine cell
secretory cell
Inhibition
sphincters+
Parasympathetic innervation
Vagus nerve
ACh
preganglionic N.
cholinergic N.
motor nucleus of vagual nerve in medulla
oblongata
myenteric and
submucosal plexuses
in the wall of gut
postganglionic N.
peptidergic
cholinergic N.ACh
Peptides
excitation
vessels
relaxation
upper parts
stomach
small intestine
ascending colon
right transverse
colon
sphincters-
ACh
preganglionic N.
cholinergic N.
sacral spinal Cord(S2--S4)
myenteric and
submucosal plexuses
in the wall of gut
postganglionic N.
peptidergic
cholinergic N.ACh
Peptides
excitation
relaxation
Pelvic nerve
lower partsleft 1/3
transverse
colon
Salivary glands
stomach
liver
pancreas
intestine
pelvic nervePelvic N
3. Intrinsic or Enteric Nervous System (ENS)
myenteric plexus: between the longitudinal
and circular muscle layers
submucosal plexus: between the middle
circular muscle layer and the mucosa
The nervous networks of neurons and nerve
fibers in the wall of gastrointestinal tract
Components:
characteristics
local reflexes
being controlled by extrinsic nerves
sympathetic parasympatheticSpinal cord
Brain sterm
myenteric
plexus
submucosal
plexus
epitheliumSensoryneurons
conditoned stimuli
Center
Long reflex
receptor plexusmuscle
gland
Short reflex
contraction
secretionUnconditioned Stimuli
Afferent N. Efferent N.
eye,nose,earⅠⅡⅧ
prevertebral
ganglia
Ⅴ. Endocrine function of gastrointestinal tract
the biggest endocrine organ
more than 40 types of endocrine cells
first discovered hormone – Starling and Bayliss , 1902
mucosa ofduodenum
extract
blood
blood∥
HClSecretion of
pancreatic juice
Intestine without
nerve innervation
Ernest Starling
John Henderson: Ernest Starling and ‘Hormones’: an
historical commentary. Journal of Endocrinology
2005，184, 5-10
William Bayliss
1. Gastrointestinal Hormones:
The biologically active polypeptides secreted by
the endocrine cells （amine precursor uptake and
decarboxylation ，APUD） 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
4. Brain-gut peptide : exists both in CNS and
gastrointestinal tract
more than 20 kinds: gastrin, CCK, motilin,
neurotensin
Regulating immune function
Stimulus and Response of a few Gastrointestinal Hormones
hormone secretion effects
Gastrin Antrum,upper small
intestine
(+) Gastric juice
(+) pancreatic enzymes
(+) Gastric motility
(+) Trophic to mucosa
Secretin Upper small
intestine
(+) Pancreatic juice HCO一3
(+) Bile flow
(-) Gastric acid
CCK
cholecystokinin
Upper small
intestine
(+) Pancreatic enzyme
(+) Gallbladder
contractionI cell
G cell
S cell
GIP Upper small intestine
K cell
(-) gastric juice secretion
(-)motility of stomach
(+) insulin secretion
.
Motilin Mo cell (-/+) Gastric and small
intestinal motility
Ⅰ. Secretion of Gastric Juice
Gastric juice: the fluid secreted by the cells of the gastric
mucosa
Digestive function of Stomach
Parietal cells body HCl, intrinsic factor
Chief cells body pepsinogen
G cell antrum gastrin
Neck mucous cell antrum mucus; pepsinogen
Major exocrine glands in mucosa
oxyntic gland in the body: 4 cell types
pyloric gland in the antrum: G cell; mucous cell
mucous gland: mucus
1. Hydrochloric acid(gastric acid)
action: pepsinogen pepsin
kill bacteria
secretion of secretin
absorption of Ca2+ and Fe2+
HCl
Production: parietal cell
The components and their functions of gatric juice
Warren and Marshall discovered Helicobacter
pylori, In 1983, and got Noble prize in 2005
Gastric parietal cell BloodLumen
Cellular mechanism of HCl secretion
-Cl
Na+
ATPK+
K+
HCl is
secreted
K+
ATPProton pump
alkaline tide
HCO3
_
Cl_
CO2
H2O+
Carbonicanhydrase
H2CO3
H+
HCO3-
2. Pepsinogen:
Production: chief cell and mucous cell
pepsinogen pepsinHCl
+Activation:
Action: Hydrolyze protein
3. Mucus:
Production: epithelial cell, mucous neck
cell, pyloric gland
Action: to form mucus-bicarbonate barrier
with HCO3- that protects the gastric
epithelium from damage of H+and pepsin
HCl
HCO3-－
H+
Layer of mucus
pH2
pH7
Characteristics: glycoproteins; viscid; gel
mucosal barrier
4. Intrinsic factor:
Production: parietal cell，glycoprotein
Action: the absorption of vitamine B12 in ileum
pernicious anemia
H2
M ?
Substances that stimulate HCl secretion in the body
ACh Gastrin
Ⅱ. Regulation of gastric secretion
Histamine
Enterochromaffin-like cell
H+
cAMP
Cholinergicneuron
ACh IP3
Ca2+
G cell
Gastrin
Ca2+
IP3
paracrine
endocrine
Substances that inhibit gastric secretion in the body
secretin
somatostatin:
epidermal growth factor
Gi (-) AC cAMP
neurotensin
GIP
food
Conditoned stimuliⅠⅡⅧ
unconditioned Stimuli ⅤⅦⅨⅩ
Gastric phase
Distension of fundus ,body
Distension of antrum
Chemical stimuli
Ⅹ
Gastric
gland
Ⅹ
Mecho-chemical stimuliEntero-oxyntin
cephalic phase: large amount(30%); high acid intensity
large amount of enzymegastric phase: large amount(60%); less acid intensity
less amount of enzyme
G cell
gastrin
Regulation of gastric secretion during the digestive period
plexus
Ⅲ. Inhibition of gastric secretion during the
digestive period
In stomach:
inhibit secretion of gastrin from G cell
in the antrum of stomach
stimulate the release of somatostatin
from D cell
HCl negative feedback
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.
Factors influencing gastric emptying:
Physical and chemical characteristics of food
Liquids＞solid;
isotonic＞hypotonic or hypertonic
Carbohydrate＞protein＞fat
Driving force: Difference of pressure between
stomach and duodenum
Characteristic: discontinued
Regulation of stomach emptying
Gastric factors that promote emptying:
Stretching and chemical stimuli
vagovagal reflex
gastrin
local reflexes
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
digested degree of food
time of food staying
Small intestine is ideally
suited for absorption of
quantities of nutrients
fat-solubleVit
panreatic enzymes
stomach
Small intestine
colon
Ca2+
Mg2+
Fe2+
monosaccharidessaccharobiose
Water soluble Vit
Vit B12bile salt
bile
amino acid
glycerol,fatty acid
Absorption in the small intestine
Structural basis:
microvilli
villi
fold ofkerckring
increse ofsurface area
surface areacm2
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
FAs enter cells by diffusion
• Triglyceride synthesis
• Add protein
• Chylomicrons
• To lacteal (lymph)
• Short FAs diffuse into
blood
Defecation
A reflex initiated by the stimulation of strech
receptors in the rectum
The elimination of fecal waste through the anus
Prarsympathetic N.
Pudendal N.
Pelvic N.
S2-4
contraction of rectal muscles
relaxation of the internal anal
sphincter
relaxation of the external anal
sphincter.
Pudendal N.
hypogastric 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
❖In clinic, some drugs inhibiting the H+ secretion of
stomach are used to treat gastric or duodenal ucler.
Can you design some drugs for this.
❖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
Digestive glands:
Large ~: salivary gland ,liver
pancreas
Small ~: gastric glands ,
intestinal glands
Enzyme Produced In Site of Release pH Level
Carbohydrate Digestion:
Salivary amylase Salivary glands Mouth Neutral
Pancreatic amylase Pancreas Small intestine Basic
Maltase Small intestine Small intestine Basic
Protein Digestion:
Pepsin Gastric glands Stomach Acidic
Trypsin Pancreas Small intestine Basic
Peptidases Small intestine Small intestine Basic
Nucleic Acid Digestion:
Nuclease Pancreas Small intestine Basic
Nucleosidases Pancreas Small intestine Basic
Fat Digestion:
Lipase Pancreas Small intestine Basic
• 大纲要求Teaching guide
• 内容组织Teaching content：有限时间，重点讲规律
• 启发思维develop the mind and creativity ：
• Helicobacter pylori; How to protect stomach
• Drug for inhibiting the secretion of HCl
• Process of digestion for your breakfast ( milk, egg, bread)
• Why do you feel hunger at noon
discovery of secretin
clinic problem: esophagitis, acute pancreatitis，ulcer
• 难点difficulty point：bioelectrical activities and motility
• 进展new development ：CCK/gastrin receptor
Physiol Rev 86: 805– 847, 2006
• 学生问题：gastric empting rate
pyloric pump, pyloric sphincter
gastrin for gastric empting
• 病案Clinical Case ：after ileum resected回肠切除
Cholecystokinin and Gastrin Receptors
Because of the sequence similarity in their
bioactive region, CCK and gastrin share
some biological and pharmacological
effects.
Two types of CCK receptors （GPCR）
CCK-A (CCK1R“alimentary), was first
characterized in pancreatic acini from
rodents
CCK-B （CCK2R“brain”) was first found
in the brain
In the periphery, the CCK2R can be considered
as the gastrin receptor
消化道平滑肌的电活动和收缩
平滑肌肌肉收缩：
周期性phasic：有节律 ; 紧张性tonic ：持续，强度可变
电活动：RP（可波动）、慢波、锋电位
慢波：控制节律（分节运动和蠕动），受神经、激素
调节
AP：引起周期性收缩，没有twich，多个twich总和
tonic 收缩：两种说法
1. 阈下慢波达收缩阈，也可使电压门控钙通道开
2. Medical physiology: 慢波不引起钙内流
a.持续的锋电位
b.激素或其他因素使膜电位一定程度去极
c.与膜电位无关的持续钙内流，原因不清
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
