Human
p h y iology
The Digestive System
INTRODUCTION TO
THE DIGESTIVE SYSTEM
Within the lumen of the gastrointestinal tract, large food
molecules are hydrolyzed into their monomers (subunits).
These monomers pass through the inner layer, ormucosa, of
the small intestine to enter the blood or lymph in a process
called absorption.
Digestion and absorption are aided by specializations of the
gastrointestinal tract.
Functions of the GI Tract
Motility:
▫ Movement of of food through the GI tract.
Ingestion:
Taking food into the mouth.
Mastication:
Chewing the food and mixing it with saliva.
Deglutition:
Swallowing the food.
Peristalsis:
Rhythmic wave-like contractions that move food
through GI tract.
Functions of the GI Tract
(continued)
• Secretion:
▫ Includes both exocrine and endocrine secretions.
Exocrine:
HCl, H20, HC03-, bile, lipase, pepsin, amylase, trypsin,
elastase, and histamine are secreted into the lumen of
the GI tract.
Endocrine:
Stomach and small intestine secrete hormones to help
regulate the GI system.
▫ Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP, and
somatostatin.
Functions of the GI Tract
(continued)
• Digestion:
▫ Breakdown of food particles into subunits
(chemical structure change).
• Absorption:
▫ Process of the passage of digestion (chemical
subunits) into the blood or lymph.
• Storage and elimination:
▫ Temporary storage and elimination of
indigestible food.
Layers of the Gastrointestinal Tract
The GI tract from the esophagus to the anal canal is composed
of four layers, or tunics.
Each tunic contains a dominant tissue type that performs
specific functions in the digestive process.
The four tunics of the GI tract, from the inside out, are the
mucosa, submucosa, muscularis, and serosa
Digestive System (GI)
• GI tract divided
into:
▫ Alimentary
canal.
▫ Accessory
digestive
organs.
• GI tract is 30 ft
long and
extends from
mouth to anus.
Insert fig. 18.2
Layers of GI Tract
• Composed of 4 tunics:
▫ Mucosa.
▫ Submucosa.
Muscularis.
Serosa.
Mucosa
• Lines the lumen of GI tract.
▫ Consists of simple columnar epithelium.
• Lamina propria:
▫ Thin layer of connective tissue containing lymph
nodules.
• Muscularis mucosae:
▫ Thin layer of smooth muscle responsible for the
folds.
Folds increase surface area for absorption.
• Goblet cells:
▫ Secrete mucus.
Submucosa
• Thick, highly vascular layer of connective
tissue.
• Absorbed molecules enter the blood and
lymphatic vessels.
• Submucosal plexus (Meissner’s plexus):
▫ Provide autonomic nerve supply to the
muscularis mucosae.
Muscularis
• Responsible for segmental contractions and
peristaltic movement through the GI tract.
▫ Inner circular layer of smooth muscle.
▫ Outer longitudinal layer of smooth muscle.
• Contractions of these layers move food
through the tract; pulverize and mix the food.
• Myenteric plexus located between the 2
muscle layers.
▫ Major nerve supply to GI tract.
Fibers and ganglia from both sympathetic and
parasympathetic nervous systems.
Serosa
• Binding and protective outer layer.
• Consists of areolar connective tissue covered
with simple squamous epithelium.
Regulation of the GI Tract
• Extrinsic innervation:
▫ Parasympathetic nervous system:
Vagus and spinal nerves:
Stimulate motility and GI secretions.
▫ Sympathetic nervous system:
Postganglionic sympathetic fibers that pass
through submucosal and myenteric plexuses and
innervate GI tract:
Reduce peristalsis and secretory activity.
Regulation of the GI Tract
(continued)
• Enteric nervous system:
▫ Sites where parasympathetic fibers synapse with
postganglionic neurons that innervate smooth muscle.
• Submucosal and myenteric plexuses:
▫ Local regulation of the GI tract.
• Paracrine secretion:
▫ Molecules acting locally.
• Hormonal secretion:
▫ Secreted by the mucosa.
From Mouth to Stomach
• Mastication (chewing):
▫ Mixes food with saliva which contains salivary
amylase.
Enzyme that can catalyze the partial digestion of starch.
• Deglutition (swallowing):
▫ Begins as a voluntary activity.
▫ Involves 3 phases:
Oral phase is voluntary.
Pharyngeal and esophageal phases are involuntary.
Cannot be stopped.
▫ Larynx is raised.
▫ Epiglottis covers the entrance to respiratory tract.
From Mouth to Stomach
(continued)
• Involuntary muscular contractions and
relaxations in the mouth, pharynx, larynx,
and esophagus are coordinated by the
swallowing center in the medulla.
• Esophagus:
▫ Connects pharynx to the stomach.
Upper third contains skeletal muscle.
Middle third contains a mixture of skeletal and smooth
muscle.
Terminal portion contains only smooth muscle.
Esophagus
• Peristalsis:
▫ Produced by a series of
localized reflexes in
response to distention of
wall by bolus.
• Wave-like muscular
contractions:
▫ Circular smooth muscle
contract behind, relaxes
in front of the bolus.
▫ Followed by longitudinal
contraction (shortening)
of smooth muscle.
Rate of 2-4 cm/sec.
▫ After food passes into
stomach, LES constricts.
Insert 18.4a
Stomach
• Most distensible part of GI tract.
▫ Empties into the duodenum.
• Functions of the stomach:
▫ Stores food.
▫ Initiates digestion of proteins.
▫ Kills bacteria.
▫ Moves food (chyme) into intestine.
Stomach
• Contractions
of the
stomach
churn
chyme.
▫ Mix chyme
with gastric
secretions.
▫ Push food
into
intestine.
(continued)
Insert fig. 18.5
Stomach
• Gastric mucosa
has gastric pits
in the folds.
• Cells that line
the folds
deeper in the
mucosa, are
gastric glands.
(continued)
Insert fig. 18.7
Gastric Glands
• Secrete gastric juice:
▫
▫
▫
▫
Goblet cells: mucus.
Parietal cells: HCl and intrinsic factor.
Chief cells: pepsinogen.
Enterochromaffin-like cells (ECL): histamine
and serotonin.
▫ G cells: gastrin.
▫ D cells: somatostatin.
▫ Stomach: ghrelin.
HCl Production
• Parietal cells
secrete H+into
gastric lumen by
primary active
transport,
through H+/ K+
ATPase pump.
• Parietal cell’s
basolateral
membrane takes
in Cl- against its
electrochemical
gradient, by
coupling its
transport with
HC03-.
Insert fig. 18.8
HCl Production
(continued)
• HCl production is stimulated:
▫ Indirectly by gastrin.
▫ Indirectly by ACh.
• ACh and gastrin stimulate release of
histamine.
▫ Histamine:
Stimulates parietal cells to secrete HCl.
HCl Functions
• Makes gastric
juice very acidic.
▫ Denatures ingested
proteins (alter
tertiary structure)
so become more
digestible.
• Activates
pepsinogen to
pepsin.
▫ Pepsin is more
active at pH of 2.0.
Insert fig. 18.9
Digestion and Absorption in the Stomach
• Proteins partially digested by pepsin.
• Carbohydrate digestion by salivary amylase is
soon inactivated by acidity.
• Alcohol and aspirin are the only commonly
ingested substances absorbed.
Gastric and Peptic Ulcers
• Peptic ulcers:
▫ Erosions of the mucous membranes of the stomach or
duodenum produced by action of HCl.
• Zollinger-Ellison syndrome:
▫ Ulcers of the duodenum are produced by excessive gastric
acid secretions.
• Helicobacter pylori:
▫ Bacterium that resides in GI tract that may produce ulcers.
• Acute gastritis:
▫ Histamine released by tissue damage and inflammation
stimulate further acid secretion.
Protective Mechanisms of Stomach
• Parietal and chief cells impermeable to HCl.
• Alkaline mucus contains HC03-.
• Tight junctions between adjacent epithelial
cells.
• Rapid rate of cell division (entire epithelium
replaced in 3 days).
• Prostaglandins inhibit gastric secretions.
Small Intestine
• Each villus is a fold in
the mucosa.
• Covered with columnar
epithelial cells
interspersed with goblet
cells.
• Epithelial cells at the
tips of villi are exfoliated
and replaced by mitosis
in crypt of Lieberkuhn.
• Lamina propria contain
lymphocytes, capillaries,
and central lacteal.
Insert fig. 18.12
Absorption in Small Intestine
• Duodenum and jejunum:
▫ Carbohydrates, amino acids, lipids, iron, and Ca2+.
• Ileum:
▫ Bile salts, vitamin B12, electrolytes, and H20.
Intestinal Enzymes
• Microvilli contain brush border enzymes
that are not secreted into the lumen.
▫ Brush border enzymes remain attached to the
cell membrane with their active sites exposed to
the chyme.
• Absorption requires both brush border
enzymes and pancreatic enzymes.
Intestinal Contractions and Motility
• 2 major types of
contractions occur in the
small intestine:
▫ Peristalsis:
Slow movement.
Pressure at the pyloric end of
small intestine is greater
than at the distal end.
▫ Segmentation:
Major contractile activity of
the small intestine.
Contraction of circular
smooth muscle.
Mix chyme.
Insert fig. 18.14
Contractions of Intestinal Smooth Muscles
• Occur automatically in
response to
endogenous pacemaker
activity.
• Rhythm of contractions
is paced by graded
depolarizations called
slow waves.
▫ Slow waves produced by
interstitial cells of Cajal.
▫ Slow waves spread from 1
smooth muscle cell to
another through nexuses.
Insert fig. 18.15
Contractions of Intestinal Smooth Muscles
• When slow waves above threshold, it triggers
APs by opening of VG Ca2+channels.
• Inward flow of Ca2+:
▫ Produces the upward depolarization phase.
▫ Stimulates contraction of smooth muscle.
• Repolarization:
▫ VG K+channels open.
Slow waves decrease in amplitude as they are conducted.
• May stimulate contraction in proportion to
the magnitude of depolarization.
Cells and Electrical Events in the Muscular is
Insert fig. 18.16
Large Intestine
• Outer surface bulges outward to form haustra.
• Little absorptive function.
▫ Absorbs H20, electrolytes, several vitamin B complexes, vitamin
K, and folic acid.
Intestinal microbiota produce significant amounts of folic acid and
vitamin K.
Bacteria ferment indigestible molecules to produce short-chain fatty
acids.
Does not contain villi.
• Secretes H 0, via active transport of NaCl into
2
intestinal lumen.
▫ Guanylin stimulates secretion of Cl- and H20, and inhibits
absorption of Na+(minor pathway).
Membrane contains Na+/K+ pumps.
▫ Minor pathway.
Fluid and Electrolyte Absorption in the
Intestine
• Small intestine:
▫ Most of the fluid and electrolytes are absorbed by
small intestine.
Absorbs about 90% of the remaining volume.
▫ Absorption of H20 occurs passively as a result of the
osmotic gradient created by active transport.
Aldosterone stimulates NaCl and H20 absorption in the
ileum.
• Large intestine:
▫ Absorbs about 90% of the remaining volume.
Absorption of H20 occurs passively as a result of the osmotic
gradient created by active transport of Na+ and Cl-.
Defecation
• Waste material passes to the rectum.
• Occurs when rectal pressure rises and external
anal sphincter relaxes.
• Defecation reflex:
▫ Longitudinal rectal muscles contract to increase
rectal pressure.
Relaxation of internal anal sphincter.
▫ Excretion is aided by contractions of abdominal
and pelvic skeletal muscles.
Push feces from the rectum.
Structure of Liver
• Liver largest internal organ.
▫ Hepatocytes form hepatic plates that are 1–2 cells
thick.
▫ Arranged into functional units called lobules.
• Plates separated by sinusoids.
▫ More permeable than other capillaries.
• Contains phagocytic Kupffer cells.
• Secretes bile into bile canaliculi, which are
drained by bile ducts.
Structure of Liver
(continued)
Insert fig. 18.20
Hepatic Portal System
• Products of digestion that are absorbed are
delivered to the liver.
• Capillaries drain into the hepatic portal vein,
which carries blood to liver.
▫ ¾ blood is deoxygenated.
▫ Hepatic vein drains liver.
Enterohepatic Circulation
• Compounds that
recirculate between
liver and intestine.
▫ Many compounds can
be absorbed through
small intestine and
enter hepatic portal
blood.
▫ Variety of exogenous
compounds are secreted
by the liver into the bile
ducts.
• Can excrete these
compounds into the
intestine with the bile.
Insert fig. 18.22
Major Categories of Liver Function
Bile Production and Secretion
• The liver produces and secretes 250–1500 ml of
bile/day.
• Bile pigment (bilirubin) is produced in spleen, bone
marrow, and liver.
▫ Derivative of the heme groups (without iron) from
hemoglobin.
• Free bilirubin combines with glucuronic acid and
forms conjugated bilirubin.
▫ Secreted into bile.
• Converted by bacteria in intestine to urobilinogen.
▫ Urobilogen is absorbed by intestine and enters the hepatic
vein.
Recycled, or filtered by kidneys and excreted in urine.
Metabolism of Heme and Bilirubin
Bile Production and Secretion
• Bile acids are derivatives
of cholesterol.
▫ Major pathway of
cholesterol breakdown in
the body.
• Principal bile acids are:
▫ Cholic acid.
▫ Chenodeoxycholic acid.
Combine with glycine or
taurine to form bile salts.
Bile salts aggregate as
micelles.
• 95% of bile acids are
absorbed by ileum.
(continued)
Insert fig. 18.25
Detoxification of the Blood
• Liver can remove hormones, drugs, and other
biologically active molecules from the blood
by:
▫ Excretion into the bile.
▫ Phagocytosis by Kupffer cells.
▫ Chemical alteration of the molecules.
Ammonia is produced by deamination of amino acids in
the liver.
Liver converts it into urea.
Excreted in urine.
Detoxification of the Blood
(continued)
• Inactivation of steroid hormones and drugs.
▫ Conjugation of steroid hormones and
xenobiotics make them anionic.
Can be transported into bile by multispecific
organic anion transport carriers.
▫ Steroid and xenobiotic receptors stimulate
production of cytochrome P450 enzymes.
Secretion of Glucose, Triglycerides and
Ketones
• Liver helps regulate blood glucose concentration
by:
▫ Glycogenesis and lipogenesis.
▫ Glycogenolysis and gluconeogenesis.
• Contains enzymes required to convert free fatty
acids into ketone bodies.
Production of Plasma Proteins
• Albumin and most of the plasma globulins
(except immunoglobulins) are produced
by the liver.
• Albumin:
▫ Constitutes 70% of the total plasma protein.
Contributes most to the colloid osmotic pressure in the
blood.
• Globulins:
▫ Transport cholesterol and hormones.
▫ Inhibit trypsin.
▫ Produce blood clotting factors I, II, III, V, VII,
IX, XI.
Gallbladder
• Sac-like organ attached to the inferior surface of
the liver.
• Stores and concentrates bile.
• When gallbladder fills with bile, it expands.
▫ Contraction of the muscularis layer of the gallbladder,
ejects bile into the common bile duct into duodenum.
• When small intestine is empty, sphincter of Oddi
closes.
▫ Bile is forced up to the cystic duct to gallbladder.
Pancreas
• Exocrine:
▫ Acini:
Secrete
pancreatic
juice.
• Endocrine:
▫ Islets of
Langerhans:
Secrete
insulin and
glucagon.
Insert fig. 18.26
Pancreatic Juice
• Contains H 0, HC0
2
3
and digestive enzymes.
Pancreatic Juice
• Complete digestion of
food requires action of
both pancreatic and
brush border enzymes.
▫ Most pancreatic
enzymes are produced
as zymogens.
▫ Trypsin (when activated
by enterokinase) triggers
the activation of other
pancreatic enzymes.
• Pancreatic trypsin
inhibitor attaches to
trypsin.
▫ Inhibits its activity in
the pancreas.
Fig. 18.29
Neural and Endocrine Regulation
• Neural and endocrine mechanisms modify the
activity of the GI system.
• GI tract is both an endocrine gland, and a target
for the action of hormones.
Regulation of Gastric Function
• Gastric motility and secretion are automatic.
• Waves of contraction are initiated
spontaneously by pacesetter cells.
• Extrinsic control of gastric function is divided
into 3 phases:
▫ Cephalic phase.
▫ Gastric phase.
▫ Intestinal phase.
Cephalic Phase
• Stimulated by sight, smell, and taste of food.
• Activation of vagus:
▫ Stimulates chief cells to secrete pepsinogen.
▫ Directly stimulates G cells to secrete gastrin.
▫ Directly stimulates ECL cells to secrete
histamine.
▫ Indirectly stimulates parietal cells to secrete
HCl.
• Continues into the 1st30 min. of a meal.
Gastric Phase
• Arrival of food in stomach stimulates the gastric
phase.
• Gastric secretion stimulated by:
▫ Distension.
▫ Chemical nature of chyme (amino acids and short
polypeptides).
Stimulates G cells to secrete gastrin.
Stimulates chief cells to secrete pepsinogen.
Stimulates ECL cells to secrete histamine.
Histamine stimulates secretin of HCl.
▫ Positive feedback effect.
As more HCl and pepsinogen are secreted, more polypeptides and
amino acids are released.
Gastric Phase
(continued)
• Secretion of HCl is also
regulated by a negative
feedback effect:
▫ HCl secretion
decreases if pH < 2.5.
▫ At pH of 1.0, gastrin
secretion ceases.
D cells stimulate
secretion of
somatostatin.
Paracrine
regulator to
inhibit secretion
of gastrin.
Insert. Fig. 18.30
Intestinal Phase
• Inhibits gastric activity when chyme enters the
small intestine.
• Arrival of chyme increases osmolality and
distension.
▫ Activates sensory neurons of vagus and produces an
inhibitory neural reflex:
Inhibits gastric motility and secretion.
In the presence of fat, enterogasterone inhibits gastric
motility and secretion.
• Hormone secretion:
▫ Inhibit gastric activity:
Somatostatin, CCK, and GLP-1.
Enteric Nervous System
• Submucosal and myenteric plexuses contain
100 million neurons.
• Include preganglionic parasympathetic
axons, ganglion cell bodies, postganglionic
sympathetic axons; and afferent intrinsic and
extrinsic sensory neurons.
Enteric Nervous System
• Peristalsis:
• ACh and
substance P
stimulate smooth
muscle
contraction
above the bolus.
• NO, VIP, and
ATP stimulate
smooth muscle
relaxation below
the bolus.
(continued)
Insert fig. 18.31
Paracrine Regulators of the Intestine
• Serotonin (5-HT):
▫ Stimulates intrinsic afferents, which send impulses into
intrinsic nervous system; and activates motor neurons.
• Motilin:
▫ Stimulates contraction of the duodenum and stomach
antrum.
• Guanylin:
▫ Activates guanylate cyclase, stimulating the production of
cGMP.
cGMP stimulates the intestinal cells to secrete Cl- and H20.
Inhibits the absorption of Na+.
• Uroguanylin:
▫ May stimulate kidneys to secrete salt in urine.
Intestinal Reflexes
• Intrinsic and extrinsic regulation controlled by
intrinsic and paracrine regulators.
• Gastroileal reflex:
▫ Increased gastric activity causes increased motility of
ileum and movement of chyme through ileocecal
sphincter.
• Ileogastric reflex:
▫ Distension of ileum, decreases gastric motility.
• Intestino-intestinal reflex:
▫ Overdistension in 1 segment, causes relaxation
throughout the rest of intestine.
Secretion of Pancreatic Juice
• Secretion of pancreatic juice and bile is stimulated by:
• Secretin:
▫ Occurs in response to duodenal pH < 4.5.
▫ Stimulates production of HC03- by pancreas.
▫ Stimulates the liver to secrete HC03-into the bile.
• CCK:
▫ Occurs in response to fat and protein content of chyme
in duodenum.
▫ Stimulates the production of pancreatic enzymes.
▫ Enhances secretin.
▫ Stimulates contraction of the sphincter of Oddi.
Digestion and Absorption of
Carbohydrates
• Salivary amylase:
▫ Begins starch digestion.
• Pancreatic amylase:
▫ Digests starch to
oligosaccharides.
▫ Oligosaccharides
hydrolyzed by brush
border enzymes.
• Glucose is transported
by secondary active
transport with Na+into
the capillaries.
Insert fig. 18.32
Digestion and Absorption of Protein
• Digestion begins in the stomach when pepsin
digests proteins to form polypeptides.
• In the duodenum and jejunum:
▫ Endopeptidases cleave peptide bonds in the
interior of the polypeptide:
Trypsin.
Chymotrypsin.
Elastase.
▫ Exopeptidases cleave peptide bonds from the ends
of the polypeptide:
Carboxypeptidase.
Aminopeptidase.
Digestion and Absorption of Protein
(continued)
• Free amino acids
absorbed by
cotransport with
Na+.
• Dipeptides and
tripeptides
transported by
secondary active
transport using a
H+gradient to
transport them into
the cytoplasm.
• Hydrolyzed into
free amino acids
and then secreted
into the blood.
Insert fig. 18.33
Digestion and Absorption of Lipids
• Arrival of lipids in the duodenum serves as a
stimulus for secretion of bile.
• Emulsification:
▫ Bile salt micelles are secreted into duodenum to
break up fat droplets.
• Pancreatic lipase and colipase hydrolyze
triglycerides to free fatty acids and
monglycerides.
▫ Colipase coats the emulsification droplets and
anchors the lipase enzyme to them.
▫ Form micelles and move to brush border.
Digestion and Absorption of Lipids
(continued)
• Free fatty acids, monoglycerides, and
lysolecithin leave micelles and enter into
epithelial cells.
▫ Resynthesize triglycerides and phospholipids
within cell.
Combine with a protein to form chylomicrons.
• Secreted into central lacteals.
Transport of Lipids
• In blood, lipoprotein lipase hydrolyzes
triglycerides to free fatty acids and glycerol for
use in cells.
• Remnants containing cholesterol are taken to
the liver.
▫ Form VLDLs which take triglycerides to cells.
▫ Once triglycerides are removed, VLDLs are
converted to LDLs.
LDLs transport cholesterol to organs and blood vessels.
• HDLs transport excess cholesterol back to
liver.
Absorption of Fat