gastrointestinal physiology yue limin( 岳利民 ) department of physiology school of preclinical...

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