Overview of Gastrointestinal Function

Overview of Gastrointestinal Function
George N. DeMartino, Ph.D.
Department of Physiology
University of Texas Southwestern Medical Center
Dallas, TX 75390
The gastrointestinal system
Functions of the
gastrointestinal system
•
Digestion
•
Absorption
•
Secretion
•
Motility
•
Immune surveillance
and tolerance
GI-OP-13
Histology of the GI tract
Blood
or
Serosal Side
Lumenal
or
Mucosal Side
Structure of a villus
Villus
Lamina propria
Movement of substances across the epithelial layer
X
Tight junctions
Lumen
Apical
membrane
X
Blood
Basolateral
membrane
X
transcellular
X
X
paracellular
GI-OP-19
Histology of the GI tract
Blood
or
Serosal Side
Lumenal
or
Mucosal Side
Motility in the gastrointestinal system
Propulsion
net movement by peristalsis
Mixing
for digestion and absorption
Separation
sphincters
Storage
decreased pressure
GI-OP-42
Intercellular signaling in the
gastrointestinal system
•
Neural
•
Hormonal
•
Paracrine
GI-OP-10
Neural control of the GI system
•
Extrinsic nervous system
autonomic central nervous system
•
Intrinsic (enteric) nervous system
entirely with the GI system
GI-OP-14
The extrinsic nervous system
The intrinsic nervous system forms
complete functional circuits
Sensory neurons
Interneurons
Motor neurons
(excitatory and
inhibitory)
Y
Parasympathetic nerves regulate functions
of the intrinsic nervous system
Reflex control of gastrointestinal functions
Vago-vagal
reflex
Afferent
Salivary Glands
Composition of Saliva
O Proteins
α−amylase
lipase
lysozyme
mucus
lactoferrin
RNase
et al
O Electrolyte solution
water
Na+ , K +
HCO3-
Functions of saliva
•
Oral protection
•
Oral hygiene
•
Lubrication
•
Digestion
buffering of hot, cold, acid, base
bacteriostatic
swallowing
carbohydrates and lipids
GI-ME-11
Structure of the esophagus
Pharynx
Upper
Esophageal
Sphincter
(UES)
Skeletal
muscle
Skeletal
and smooth
muscle
Smooth
muscle
Diaphragm
Lower
Esophageal
Sphincter
(LES)
Stomach
GI-010
Regulation of the UES during a swallow
Reflex
relaxation
(neural)
Reflex
contraction
(neural)
Persistalsis
Regulation of the UES during a swallow
Reflex
relaxation
(neural)
VIP
(NO ?)
Reflex
contraction
(myogenic)
Anatomical and functional
divisions of the stomach
LES
Pyloric
gland
area
Fundus
Orad
Gastric
juice
pylorus
Oxyntic
gland
G cell
Caudad
duodenum
Oxyntic
gland
area
Gastrin
Antrum
Body
(Corpus)
GI-S-15
Mechanism of acid secretion by the parietal cell
H2O
Lumen Cl-
K+
H2O
K+
Na+
H+
Cl-
ATP
ADP
K+
Cl-
ATP
ADP
Na+ H20
H+ + OH CO2
Blood
+
HCO3Carbonic
anhydrase
GI-S-07
Stimulation of acid secretion in parietal cells
Receptors
Histamine (H2)
G
Gastrin
G
ACh
AC
PL-C
PL-C
G
+
H
H+
Lumen
GI-S-13
Stimulation of acid secretion in parietal cells
Receptors
Histamine (H2)
G
Gastrin
G
ACh
AC
PL-C
PL-C
G
cAMP
Protein kinase A
Sequestered
H+ / K+ pumps
IP3 + DAG
Ca2+
Substrates
Membrane-exposed
H+ / K+ pumps
Protein kinase
C
Substrates
H+
Lumen
Sequestered
H+ / K+ pumps
GI-S-13
Cephalic phase
of acid secretion
vagal nucleus
vagus nerve
thought, sight, smell,
taste, or chewing of food
H+
ACh
GRP
Parietal cell
ECL cell
G cell
Histamine
Gastrin
Efferent pathways
circulation
GI-S-05
vagal nucleus
Gastric phase
of acid secretion
vagus nerve
distension sensed
by mechanoreceptors
distension in the stomach,
presence of amino acids
and peptides
H+
Amino acids
and peptides
ACh
G cell
GRP
ACh
Efferent pathways
Afferent pathways
Parietal cell
ECL cell
Histamine
Gastrin
circulation
GI-S-06
Protection of the epithelial lining of the stomach
pH 2
HCO3-
HCO3-
Gastric lumen
Mucus layer
pH 7
Mucus
GI-S-19
Motility in the stomach
•
Reservoir
storage without increased pressure
•
Grinding and mixing
mechanical disruption for digestion and
absorption
•
Regulated pumping
optimal delivery to duodenum
GI-S-32
The gastrointestinal system
Small Intestine
Digestion
Absorption
Secretion
Motility
Pancreatic Secretion
Aqueous Component (ductule cells)
water
bicarbonate
Function: acid neutralization
Enzymatic Component (acinar cells)
proteases
lipases
saccharidases
Function: digestion
Intestinal phase
of pancreatic secretion
vagal nucleus
vagus nerve
afferent
pathways
for vagal
reflex
acid and digestion products
in the duodenum
protein
I cells
amino acids
peptides
fat
H+
S cells
circulation
CCK
efferent
pathways for
vagal reflex
HCO3H2O
Secretin
Ach
Enzymes
ductule cells
pancreas
acinar cells
GI-SILPGB-02
Secretion from the liver and gallbladder
Figure15
Na+ Cl - K+
Liver
Ca2+
Bile
acids
water
Portal
circulation
Figure11
Secretin
HCO3Na+
H20
Gallbladder
HCO3ClNa+
H20
CCK
Sphincter of Oddi
Bile
Duodenum
Figure14
Ach
Bile acids
Ileum
Functions of Bile
• Emulsification of dietary lipids
required for lipid digestion
• Solubilization of lipid digestion products
required for lipid absorption
• Excretion of waste products
bilirubin and cholesterol
GI-SILPGB-30
Organic components of bile
•
Bile acids / bile salts
70%
•
Phospholipids
20%
•
Cholesterol
5%
•
Bilirubin
1%
•
Everything else
4%
GI-SILPGB-40
Components of bile
Bile acids package products of lipid digestion
into mixed micelles for absorption
Products of lipid digestion
Cholesterol
+
--
+
--
Lysolecithin
Monoglyceride
+
Free fatty acid
--
-
+
Mixed micelle
-
GI-SILPGB-36
Digestion and absorption in the small intestine
Proteins
degradation to amino acids and peptides
combined action of lumenal and membranebounds proteases
absorption by multiple transporters
Carbohydrates
degradation to monosaccharides
combined action of lumenal and membranebounds proteases
absorption by several transporters
Lipids
Absorption of monosaccharides
in the small intestine
Na+/ K+ ATPase
K+
SGLT1
ATP¤ADP
Na+
Glucose /
Galactose
Na+
Fructose
Fructose
Glucose /
Galactose
Glut 2
Glut 5
Lumen
(Apical)
Blood
(Basolateral)
GI-SILPGB-16
Fluid balance in the GI tract
~ 20% total
body water !
9000 ml
8900 ml
Volume
entering
intestines
Volume
absorbed
by
intestines
100 ml
Volume
excreted
Important Principle
The absorption of water
is dependent on and
proportional to
the absorption of solutes
GI-LI-25
Bad things happen when solutes are not absorbed
Jejunum
Lactose
Ileum
Colon
Na+
glucose + galactose H2O
H2O
Normal
SCFA
Lactose
Lactose H2O
CO2
Diarrhea
Lactose
H2O
Lactase deficiency
H2O
GI-LI-24