Chapter 18
Lecture
Outline
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Chapter 18 Outline
Introduction to the Digestive System
From Mouth to Stomach
Small Intestine
Large Intestine
Liver, Gall Bladder, and Pancreas
Neural and Endocrine Regulation of the
Digestive System
Digestion and Absorption of Carbohydrates,
Lipids, and Proteins
18-2
Introduction to the Digestive System
Inside
gastrointestinal (GI) tract, food is broken down
by hydrolysis into molecular monomers
Absorption of monomers occurs in small intestine
18-3
18-4
Functions of GI Tract
18-5
Motility
Is
movement of food through GI tract by means of:
Ingestion--taking food into mouth
Mastication--chewing food and mixing it with saliva
Deglutition--swallowing food
Peristalsis--rhythmic wave-like contractions that
move food through GI tract
18-6
Secretion
Includes
release of exocrine and endocrine products
into GI tract
Exocrine secretions include: HCl, H2O, HCO3-, bile,
lipase, pepsin, amylase, trypsin, elastase, and
histamine
Endocrine includes hormones secreted into stomach
and small intestine to help regulate GI system
e.g. gastrin, secretin, CCK, GIP, GLP-1, guanylin,
VIP, and somatostatin
18-7
Digestion
Refers to breakdown of food molecules into smaller
subunits
Absorption
Is
passage of digested end products into blood or
lymph
18-8
Storage and Elimination
Includes
temporary storage and subsequent
elimination of indigestible components of food
Immune Barrier
Includes physical barrier formed by tight junctions between
cells of small intestine
And cells of the immune system that reside in connective
tissue just below epithelium
18-9
Structure of Digestive System
18-10
Digestive System
Is
composed of GI tract (alimentary canal) and
accessory digestive organs
GI tract is 30 ft long; extends from mouth to anus
18-11
Digestive System continued
 Organs
include oral
cavity, pharynx,
esophagus,
stomach, and small
and large intestine
 Accessory organs
include teeth,
tongue, salivary
glands, liver,
gallbladder, and
pancreas
18-12
Layers of GI Tract
Are
called tunics
The 4 tunics are mucosa, submucosa, muscularis, and
serosa
18-13
Mucosa
 Is
the absorptive and secretory layer lining lumen of GI tract
 In places is highly folded with villi to increase absorptive area
 Contains lymph nodules, mucus-secreting goblet cells, and thin
layer of muscle
18-14
Submucosa
 Is
a thick, highly vascular layer of connective tissue where
absorbed molecules enter blood and lymphatic vessels
 Contains glands and nerve plexuses (submucosal plexus) that
carry ANS activity to muscularis mucosae of small and large int.
18-15
Muscularis
Is
responsible for segmental contractions and
peristaltic movement through GI tract
Has an inner circular and outer longitudinal layer of
smooth muscle
Activity of these layers moves food through tract
while pulverizing and mixing it
Myenteric plexus between these layers is major
nerve supply to GI tract
Includes fibers and ganglia from both Symp and
Parasymp systems
18-16
Serosa
 Is
outermost layer; serves to bind and protect
 Consists of areolar connective tissue covered with layer of
simple squamous epithelium
18-17
Regulation of GI Tract
Parasympathetic
effects, arising from vagus and spinal
nerves, stimulate motility and secretions of GI tract
Sympathetic activity reduces peristalsis and secretory
activity
GI tract contains an intrinsic system that controls its
movements--the enteric nervous system
GI motility is influenced by paracrine and hormonal
signals
18-18
From Mouth to Stomach
18-19
From Mouth to Stomach
Mastication
(chewing) mixes food with saliva which
contains salivary amylase
An enzyme that catalyzes partial digestion of starch
18-20
From Mouth to Stomach continued
Deglutition
(swallowing) begins as voluntary activity
Oral phase is voluntary and forms a food bolus
Pharyngeal and esophageal phases are involuntary
and cannot be stopped
To swallow, larynx is raised so that epiglottis covers
entrance to respiratory tract
A swallowing center in medulla orchestrates
complex pattern of contractions required for
swallowing
18-21
From Mouth to Stomach continued
Esophagus
connects pharynx to stomach
Upper third contains skeletal muscle
Middle third contains mixture of skeletal and smooth
Terminal portion contains only smooth
Passes through diaphragm via esophageal hiatus
18-22
From Mouth to Stomach continued
 Peristalsis
propels food
thru GI tract
 = wave-like
muscular
contractions
 After food passes
into stomach, the
gastroesophageal
sphincter constricts,
preventing reflux
18-23
Stomach
18-24
Stomach
Is
most distensible part of GI tract
Empties into the duodenum
Functions in: storage of food; initial digestion of
proteins; killing bacteria with high acidity; moving
soupy food mixture (chyme) into intestine
18-25
Stomach continued
 Is
enclosed by
gastroesophageal
sphincter on top and
pyloric sphincter on
bottom
 Is divided into 3
regions:
 Fundus
 Body
 Antrum
18-26
Stomach continued
 Inner
surface of
stomach is highly
folded into rugae
 Contractions of
stomach churn
chyme, mixing it
with gastric
secretions
 Eventually these
will propel food
into small
intestine
18-27
Stomach continued
 Gastric
mucosa
has gastric pits in
its folds
 Cells that line
folds deeper in
the mucosa, are
exocrine gastric
glands
18-28
Stomach continued
 Gastric
glands contain cells
that secrete different
products that form gastric
juice
 Goblet cells secrete
mucus
 Parietal cells secrete
HCl and intrinsic factor
(necessary for B12
absorption in intestine)
 Chief cells secrete
pepsinogen (precursor
for pepsin)
18-29
Stomach continued
Enterochromaffin-
like cells secrete
histamine and
serotonin
G cells secrete
gastrin
D cells secrete
somatostatin
18-30
HCl in Stomach
 Is
produced by
parietal cells which
pump H+ into lumen
via an H+/ K+ pump
(pH ~1)
 Cl- is secreted by
facilitated diffusion
 H+ comes from
dissociation of
H2CO3
 Cl- comes from
blood side of cell in
exchange for HCO318-31
HCl in Stomach continued
Is
secreted in response to the hormone gastrin; and
ACh from vagus
These are indirect effects since both stimulate
release of histamine which causes parietal cells to
secrete HCl
18-32
HCl in Stomach continued
 Makes
gastric juice
very acidic which
denatures proteins
to make them more
digestible
 Converts
pepsinogen into
pepsin
 Pepsin is more
active at low pHs
18-33
Protection of Stomach Against HCL and
Pepsin
Both
HCL and pepsin can damage lining and produce
a peptic ulcer
1st line of defense is the adherent layer of mucus
= a stable gel of mucus coating the gastric
epithelium
Contains bicarbonate for neutralizing HCL
Is a barrier to actions of pepsin
Gastric epithelial cells contain tight junctions to prevent
HCL and pepsin from penetrating the surface
Gastric epithelial cells are replaced every 3 days
18-34
Digestion and Absorption in Stomach
Proteins
are partially digested by pepsin
Carbohydrate digestion by salivary amylase is soon
inactivated by acidity
Alcohol and aspirin are the only commonly ingested
substances that are absorbed
18-35
Gastric and Peptic Ulcers
 Peptic
ulcers are erosions of mucous membranes of
stomach or duodenum caused by action of HCl
 In Zollinger-Ellison syndrome, duodenal ulcers result from
excessive gastric acid in response to high levels of gastrin
 Helicobacter pylori infection is associated with ulcers
 Antibiotics are useful in treating ulcers
 And also proton pump inhibitors such as Prilosec
 Acute gastritis is an inflammation that results in acid
damage due to histamine released by inflammation
 Is why histamine receptor blockers such as Tagamet
and Zantac can treat gastritis
18-36
Small Intestine
18-37
Small Intestine (SI)
 Is
longest part of GI tract; approximately 3m long
 Duodenum is 1st 25cm after pyloric sphincter
 Jejunum is next 2/5 of length
 Ileum is last 3/5 of length; empties into large intestine
18-38
Small Intestine (SI) continued
Absorption
of digested food occurs in SI
Facilitated by long length and tremendous surface
area
18-39
Small Intestine (SI) continued
 Surface
area
increased by
foldings and
projections
 Large folds are
plicae circulares
 Microscopic fingerlike projections are
villi
 Apical hair-like
projections are
microvilli
18-40
Small Intestine (SI) continued
 Each
villus is covered with
columnar epithelial cells
interspersed with goblet
cells
 Epithelial cells at tips of
villi are exfoliated and
replaced by mitosis in
crypts of Lieberkuhn
 Inside each villus are
lymphocytes, capillaries,
and central lacteal
18-41
Small Intestine (SI) continued
A
carpet of hair-like microvilli project from apical
surface of each epithelial cell
Create a brush border
18-42
Intestinal Enzymes
Attached
to microvilli are brush border enzymes that
are not secreted into lumen
Enzyme active sites are exposed to chyme
18-43
Intestinal Contractions and Motility
2
major types of contractions
occur in SI:
 Peristalsis
is weak and
slow and occurs mostly
because pressure at
pyloric end is greater than
at distal end
 Segmentation is major
contractile activity of SI
 Is contraction of circular
smooth muscle to mix
chyme (shown in
diagram)
18-44
Intestinal Contractions and Motility continued
 Occur
automatically
via endogenous
pacemaker activity
 Contractions are
driven by graded
depolarizations
called slow waves
18-45
Intestinal Contractions and Motility continued
 Slow
waves are
produced by nonneuronal/nonmuscular cells
called interstitial
cells of Cajal (ICC)
 Have long
processes joined to
each other and to
smooth muscle via
gap junctions
 Spreads depolariz.
from one cell to
next
18-46
Intestinal Contractions and Motility continued
When
slow waves exceed threshold, trigger APs in
smooth muscle by opening V-gated Ca2+ channels
Influx of Ca2+ produces depolarization phase of AP
and stimulates contraction
Repolarization via K+ efflux
Contractions are modified by ANS activity
ACh from Parasymp increases amplitude and
duration of slow waves
Norepi and Epi from Symp decrease activity of
intestines
18-47
Large Intestine
18-48
Large Intestine (LI) or Colon
 Has
no digestive function but absorbs H2O, electrolytes, B
and K vitamins, and folic acid
 Internal surface has no villi or crypts and is not very
elaborate
 Contains large population of microflora
 = 1013 to 1014 commensal bacteria of 400 species
which produce folic acid and vitamin K and ferment
indigestible food to produce fatty acids
And reduce ability of pathogenic bacteria to infect LI
antibiotics can negatively affect commensals
18-49
Large Intestine (LI) or Colon continued
 Extends
from
ileocecal valve at
end of SI to anus
 Outer surface bulges
to form pouches
(haustra)
 Chyme from SI
enters cecum, then
passes to ascending
colon, transverse
colon, descending
colon, sigmoid colon,
rectum, and anal
canal
18-50
Fluid and Electrolyte Absorption in LI
SI
absorbs most water but LI absorbs 90% of water it
receives
Begins with osmotic gradient set up by Na+/K+
pumps
Water follows by osmosis
Salt and water reabsorption stimulated by aldosterone
LI can also secrete H2O via active transport of NaCl
into intestinal lumen
18-51
Defecation
After
electrolytes and water have been absorbed,
waste material passes to rectum, creating urge to
defecate
Defecation reflex begins with relaxation of the external
anal sphincter allowing feces to enter anal canal
Longitudinal rectal muscles contract to increase
rectal pressure; internal anal sphincter relaxes
Excretion is aided by contractions of abdominal and
pelvic muscles which push feces from rectum
18-52
Liver
18-53
Structure of Liver
 Liver
is the largest internal organ
 Hepatocytes form hepatic plates that are 1–2 cells thick
 Plates are separated by sinusoids which are fenestrated and
permeable even to proteins
 Contain phagocytic Kupffer cells
18-54
Structure of Liver continued
A
damaged liver can regenerate itself from mitosis of
surviving hepatocytes
In some cases, such as alcohol abuse or viral
hepatitis, regeneration does not occur
Can lead to liver fibrosis and ultimately cirrhosis
18-55
Hepatic Portal System
Food
absorbed in SI is delivered 1st to liver
Capillaries in digestive tract drain into the hepatic
portal vein which carries blood to liver
Hepatic vein drains liver
Liver also receives blood from the hepatic artery
18-56
Liver Lobules
 Are
functional units formed by hepatic plates
 In middle of each is central vein
 At edge of each lobule are branches of hepatic portal vein and
artery which open into sinusoids
18-57
Liver Lobules continued
 Bile
is secreted by hepatocytes in bile canaliculi
 Empty into bile ducts which flow into hepatic ducts that carry
bile away from liver
18-58
Enterohepatic Circulation
 Is
recirculation of
compounds between
liver and intestine
 Many compounds are
released in bile,
reabsorbed in SI, and
returned to liver to be
recycled
 Liver excretes drug
metabolites into bile to
pass out in feces
18-59
18-60
Bile Production and Secretion
 Amounts
to 250–1500 ml/day
 Bile pigment (bilirubin) is produced in spleen, bone
marrow, and liver
 Is a derivative of heme groups (minus iron) from Hb
 Carried in blood attached to albumin
 Free bilirubin combines with glucuronic acid to form
conjugated bilirubin that is secreted into bile
 Converted by intestinal bacteria to urobilinogen
 30-50% of urobilogen is absorbed by intestine and
enters hepatic vein
Thus enters enterohepatic circulation to be recycled
or filtered by kidneys and excreted in urine
18-61
Metabolism of Heme and Bilirubin
18-62
Bile Acids
 Are
formed in major
breakdown pathway for
cholesterol
 Are mostly cholic and
chenodeoxycholic acids
 Form bile salts by
combining with glycine
or taurine
 Bile salts aggregate
as micelles
 95% of bile acids are
absorbed by ileum
18-63
Detoxication of Blood
Liver
can remove hormones, drugs, and other
biologically active molecules from blood by:
Excretion into bile
Phagocytosis by Kupffer cells
Chemical alteration of molecules
e.g. ammonia is produced by deamination of
amino acids in liver
 Liver converts it to urea which is excreted in
urine
18-64
Detoxification of Blood continued
Liver
conjugates steroid hormones and xenobiotics
with groups that make them anionic
Which can be transported into bile or urine by
multispecific organic anion transport carriers and
excreted
Cytochrome P450 enzymes are involved in hepatic
metabolism of steroids and drugs
Stim. by activation of nuclear receptors =SXR
(steroid and xenobiotic receptor
18-65
Secretion of Glucose, Triglycerides and
Ketones
Liver
helps regulate blood glucose by removing it from
blood or releasing it to blood
Removes it via glycogenesis and lipogenesis
Or produces it via glycogenolysis and
gluconeogenesis
Can convert free fatty acids into ketone bodies
(ketogenesis) that can be used for energy during
fasting
18-66
Production of Plasma Proteins
Albumin
and most of plasma globulins are produced
by liver
Albumin makes up 70% of total plasma protein and
contributes most of the colloid osmotic pressure of
blood
Globulins transport cholesterol, triglycerides, steroid
and thyroid hormones, inhibit trypsin, and are involved
in blood clotting
Clotting factors I, II, V, VII, IX, and XI as well as
angiotensinogen all prod. by liver
18-67
Gallbladder and Pancreas
18-68
Gallbladder
 Is
a sac-like organ attached to
inferior surface of liver
 Stores and concentrates bile
continuously produced by liver
 When SI is empty, sphincter
of Oddi in common bile duct
closes and bile is forced into
gallbladder
 Expands as it fills with bile
 When food is in SI, sphincter of
Oddi opens, gall bladder
contracts, and bile is ejected thru
cystic duct into common bile
duct then to duodenum
18-69
Pancreas
Is
located behind stomach
Has both endocrine and exocrine functions
Endocrine function performed by islets of
Langerhans
Secretes insulin and glucagon
Exocrine secretions include bicarbonate solution
and digestive enzymes
These pass in pancreatic duct to SI
Exocrine secretory units are acini
18-70
Pancreatic juice and bile are secreted into the duodenum
18-71
The Pancreas is Both an Exocrine
and Endocrine Gland
(a) A photomicrograph of the
endocrine and exocrine
portions of the pancreas
(b) An illustration depicting
the exocrine acini, where
acinar cells prod. Inactive
enzymes stored as
zymogen granules which
are secreted via ducts
into duodenum
18-72
Pancreatic Juice
Contains
water, bicarbonate, and digestive enzymes
Digestive enzymes include amylase for starch, trypsin
for proteins, and lipase for fats
Brush border enzymes are also required for
complete digestion
18-73
The Activation of Pancreatic Juice Enzymes
 Most
pancreatic
enzymes are
produced in inactive
form (zymogens)
 Trypsin is activated
by brush border
enzyme,
enterokinase
 Trypsin in turn
activates other
zymogens
18-74
18-75
Neural and Endocrine Control of the
Digestive System
18-76
Neural and Endocrine Regulation
 Neural
and endocrine mechanisms modify activity of GI system
 Vagus nerve is heavily involved in regulating and
coordinating digestive activities
 GI tract is both an endocrine gland and target for action of
hormones
 Hormones include secretin, gastrin, CCK, and GIP
18-77
Regulation of Gastric Function
Gastric
motility and secretion occur automatically
Waves of contraction are initiated spontaneously by
pacesetter cells and secretion occurs in absence of
hormonal and neural input
ANS and hormonal effects are superimposed on
automatic activity
Extrinsic control of gastric function is divided into
cephalic, gastric, and intestinal phases
18-78
Cephalic Phase
Refers
to control by brain of vagus activity
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 1st 30 min of a meal
18-79
Gastric Phase
Distention
of stomach stim. vagus nerve
Vagus nerve stim. acid secretion
Amino acids and peptides in stomach lumen stim. acid
secretion
Direct stim. of parietal cells
Stim. of gastrin secretion; gastrin stim. acid
secretion
Gastrin secretion inhibited by when pH of gastric
juice falls below 2.5
18-80
Gastric Phase continued
 Short
polypeptides and
amino acids stimulate G cells
to secrete gastrin and chief
cells to secrete pepsinogen
 Gastrin stimulates ECL
cells to secrete histamine
which stimulates parietal
cell secretion of HCl
 This is a positive
feedback mechanism: As
more HCl and pepsinogen
are secreted, more
polypeptides and amino
acids are released
18-81
Gastric Phase continued
 Secretion
of HCl is also
regulated by a negative
feedback mechanism:
 HCl secretion
decreases if pH <
2.5; at pH 1 gastrin
secretion stops
 D cells stimulate
secretion of
somatostatin which
inhibits gastrin
secretion
18-82
Intestinal Phase
 Begins
when chyme enters the SI and inhibits gastric activity
 Arrival of chyme in SI is detected by sensory neurons of vagus
 This causes a neural reflex that inhibits gastric motility and
secretion
 Fat in chyme stimulates SI to secrete enterogasterones-hormones that inhibit gastric motility and secretion
 Enterogasterones include somatostatin, GIP, CCK, and
GLP-1
 GIP and GLP-1 stimulate insulin secretion in anticipation
of glucose entering blood from digestion
18-83
Enteric Nervous System
ENS
organized into ganglia interconnected by 2
plexuses:
Outer myenteric (Auerbach’s) plexus found along
entire length of GI tract
Inner submucosal (meissner’s plexus) located only
in small and large intestine
ENS contains 100 million neurons and similar diversity
of neurotransmitters as CNS
Has interneurons, sensory, autonomic, and glia
Peristalsis is controlled by enteric NS
18-84
Enteric Nervous System continued
 For
peristalsis:
 ACh and
substance P
stimulate smooth
muscle contraction
above bolus
 NO, VIP, and ATP
stimulate smooth
muscle relaxation
below bolus
18-85
Paracrine Regulators of Intestine
ECL
cells release serotonin and motilin in response to
pressure and chemical stimuli in SI
Serotonin stimulates intrinsic afferents which
activate motor neurons in intrinsic NS
Motilin stimulates contraction in duodenum and
stomach antrum
Guanylin, from ileum and colon, stimulates production
of cGMP which inhibits absorption of Na+and causes
secretion of Cl- and H2O
Uroguanylin found in urine---appears to be prod. by
intestines and may function as hormone that stim.
kidneys to excrete salt in urine
18-86
Intestinal Reflexes
Can
be mediated by enteric NS and paracrines; and
regulated by ANS and hormones
Gastroileal reflex refers to increased motility of ileum
and movement of chyme thru ileocecal sphincter in
response to increased gastric activity
Ileogastric reflex decreases gastric motility in response
to distension of ileum
Intestino-intestinal reflex causes relaxation of rest of
intestine when any part is overdistended
18-87
Secretion of Pancreatic Juice
Secretion
of pancreatic juice is stimulated by secretin
and CCK (cholecystokinin)
Secretin is secreted in response to duodenal pH < 4.5
Stimulates release of HCO3- into SI by pancreas
CCK is secreted in response to fat and protein content
of chyme in duodenum
Stimulates production of pancreatic enzymes
Enhances secretin
Stimulates contraction of sphincter of Oddi
18-88
Digestion and Absorption of
Carbohydrates, Lipids, and Proteins
18-89
The Action of Pancreatic Amylase
 Most
carbohydrates are
ingested as starch-a polymer of glucose
 Salivary amylase begins
starch digestion
 Pancreatic amylase
converts starch to
oligosaccharides
 Oligosaccharides
hydrolyzed by SI
brush border
enzymes
18-90
Digestion and Absorption of Protein
Begins
in stomach when pepsin digests proteins to
form polypeptides
In SI, the pancreatic juice enzymes endopeptidases
(trypsin, chymotrypsin, elastase) cleave peptide bonds
in interior of polypeptides
SI exopeptidases (carboxypeptidase -pancreatic juice
and aminopeptidase- brush border enzyme) cleave
peptide bonds from ends of polypeptides
Results in free amino acids, dipeptides, and tripeptides
Free amino acids absorbed by cotransport with Na+
into epith. cells and secreted into blood caps.
Di- and tripeptides carried into epith. cell where
hydrolyzed into free amino acids then secreted
18-91
Digestion and Absorption of Protein continued
 Protein
digestion in
SI results in free
amino acids,
dipeptides, and
tripeptides
 Which are
transported into
SI cells where diand tripeptides
are broken down
to amino acids
 Which are
secreted into
blood
18-92
Digestion and Absorption of Lipids
Occurs
in SI
Arrival of lipids in duodenum causes secretion of bile
Fat is emulsified by bile salt micelles
Forms tiny droplets of fat dissolved in bile salt
micelles
Greatly increases surface area for fat digestion
18-93
Digestion of Triglycerides
 Pancreatic
lipase
hydrolyzes
triglycerides to free
fatty acids and
monglycerides
 Phospholipase A
breaks down
phospholipids into
fatty acids and
lysolecithin
18-94
Fat Digestion and Emulsification
Products
of fat digestion dissolve in micelles forming
mixed micelles which move to brush border
18-95
The Absorption of Fat
 Free
fatty acids, monoglycerides, and lysolecithin leave micelles
and enter epithelial cells
 Inside epithelial cells, they are resynthesized into
triglycerides and phospholipids
18-96
Digestion and Absorption of Lipids continued
Triglycerides
and phospholipids combine with a protein
to form small particles called chylomicrons
Which are secreted into central lacteals of SI villi
18-97
Transport of Lipids
In
blood, chylomicrons combine with apolipoprotein
Which allows them to bind to receptors on
capillaries in muscle and fat
There endothelial lipoprotein lipase hydrolyzes
the triglycerides to free fatty acids and glycerol for
energy use by muscle and storage in fat
Cholesterol-containing remnants are taken up by
liver
18-98
Transport of Lipids continued
Cholesterol
and triglycerides from liver form VLDLs
which are secreted and take triglycerides to cells
Once triglycerides are removed, VLDLs become
LDLs
LDLs transport cholesterol to organs and blood
vessels
HDLs transport excess cholesterol back to liver
High ratio of HDL-cholesterol to total cholesterol
is believed to confer protection against
atherosclerosis
18-99