Gastrointestinal physiology
Yue Limin(岳利民 )
Department of PhysiologySchool of Preclinical and Forensic Medicine
Sichuan University
The 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
high extensibility
tonicitySensitive for chemical, thermal and mechanical stretch stimulation
slow contractility
2. Electrophysiological characteristics
Slow wave potential
Action potential
Resting potential
Resting potential of smooth muscle IN GIResting 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
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
BER AP Muscle ContractionRP
frequencydirectionspeed
strength
3. Basic types of movements in digestive tractmastication and swallowing:
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.
contraction
relaxation
Peristalsis
Segmentation contraction
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,dextrinmaltotriose
Gastric juice
pepsin protein polypeptide
Pancreticjuice
a-amylase
lipase
starchmaltose, dextrinmaltotriose
triglycerides monoglyceridefatty acids
trypsinchymotrypsincarboxypolypeptidase
polypeptideamino acid
proteinpolypeptides
bile no enzymebile 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 and lumbar spinal cord segments (T5—L2)
Preganglionic N.Cholinergic N.
enteric neuronsmooth muscleendocrine cell
secretory cellInhibition
sphincters+
Parasympathetic innervationVagus 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
excitationvesselsrelaxationupper parts
stomachsmall intestineascending colonright transversecolon
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 1/3transverse 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:
characteristicslocal reflexesbeing controlled by extrinsic nerves
sympathetic parasympatheticSpinal cordBrain sterm
myentericplexus
submucosalplexus
epithelium Sensory neurons
conditoned stimuliconditoned stimuli
Center Center
Long reflex
receptor plexus musclegland
Short reflex
contractionsecretionUnconditioned Stimuli
Afferent N. Efferent N.
eye,nose,ear eye,nose,earⅠⅡⅧ
Ⅴ. Endocrine function of gastrointestinal tract
the biggest endocrine organmore than 40 types of endocrine cellsfirst discovered hormone – Starling and Bayliss , 1902
Mucosa ofduodenum
extract
blood
blood ∥HCl
Secretion of pancreatic juice
Intestine without nerve innervation
Ernest Starling
John Henderson: Ernest Starling and ‘Hormones’: anhistorical commentary. Journal of Endocrinology 2005 , 184, 5-10
William Bayliss
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 HormonesRegulating 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
CCKcholecystokinin
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,Hp 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 tideHCO3
_
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
4. Intrinsic factor:
Production: parietal cell , glycoprotein
Action: the absorption of vitamine B12 in ileumpernicious anemia
H2
M ?
Substances that stimulate HCl secretion in the body
ACh Gastrin
Ⅱ. Regulation of gastric secretion
Histamine
Enterochromaffin- like cell
H+
cAMP
Cholinergic neuron
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 cAMPneurotensin
GIP
food
ceph
alic
phas
e Conditoned stimuli
center
ⅠⅡⅧ
unconditioned Stimuli ⅤⅦⅨⅩ
Gastric phase
Distension of fundus ,body
Distension of antrum
Chemical stimuli
Ⅹ
Gastricgland
Ⅹ
Intestinal phase
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 stomachstimulate 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 emptyingDefinition: The process that the gastric contents are delivered to the duodenum.
Factors influencing gastric emptying:
Physical and chemical characteristics of foodLiquids > solid; isotonic > hypotonic or hypertonic
Carbohydrate > protein > fat
Driving force: Difference of pressure between stomach and duodenumCharacteristic: 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
AbsorptionThe 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 B12 bile salt
bile
amino acidglycerol,fatty acid
Absorption in the small intestineStructural basis:
microvilli
villi
fold ofkerckring
increse ofsurface area
surface area cm2
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 endocytosisexocytosis 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
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.
S2-4contraction of rectal muscles
relaxation of the internal anal sphincter
relaxation of the external anal sphincter.
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.
ProblemsExplain: 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
hormonesDescribe 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