Gastrointestinal Physiology-A Global Overview

Gastrointestinal Physiology:
A Global Overview
Prepared and presented by

Marc Imhotep Cray, M.D.
Image Plates from: Klatt EC. Ch.7 - The Gastrointestinal Tract : In: Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia. PA : Saunders, 2015; 193-200.
nml stomach, gross nml stomach, endoscopy nml esophagus, micro
nml transverse
Marc Imhotep Cray, M.D. colon, endoscopy nml esophagus, endoscopy nml sm intestine and mesentery, gross
Photo: Colorized computed tomographic (CT) scan of an axial section through the abdomen. The image shows a gallstone (pink) obstructing the bile duct where it leaves the gallbladder (green
circle). The large yellow region around the gallbladder is the liver. a spine vertebra (pink) is visible in bottom center, with C-shaped kidneys (yellow) on either side. 3
From: Seeley’s Anatomy & Physiology 10th ed New York, NY: McGraw-Hill 2010
Learning outcomes
After studying this presentation, you should be able to:
1. List the functions of the digestive system.
2. Describe the microscopic structure of the gastrointestinal tract.
3. Describe the structure and functions of the esophagus and stomach.
4. Describe the composition and actions of gastric juice and explain how
gastric secretion is regulated.
5. Describe the structure and functions of the small intestine.
6. Identify the location and describe the functions of the digestive enzymes
of the small intestine.
7. Describe the muscle contractions and movements of the small intestine.
8. Describe the structure and functions of the large intestine.
9. Explain the nature and significance of the intestinal microbiota.
Marc Imhotep Cray, M.D. 4

Learning outcomes cont.
After studying this presentation, you should be able to:
10. Describe the structure and functions of the liver.
11. Describe the synthesis, composition, and functions of bile and explain
the enterohepatic circulation.
12. Describe the composition of pancreatic juice and explain the significance
of pancreatic juice enzymes.
13. Identify the phases and explain the mechanisms of gastric regulation.
14. Explain the regulation of pancreatic juice and bile secretion.
15. Explain the significance of the enteric nervous system.
16. Describe the processes involved in the digestion and
absorption of carbohydrates and proteins.
17. Describe the processes involved in the digestion, absorption, and
transport of dietary lipids.
Functions of the GI Tract
 Motility:
 Movement of food through GI tract
oIngestion:
• Taking food into the mouth
oMastication:
• Chewing food and mixing it with saliva
oDeglutition:
• Swallowing food
oPeristalsis:
• Rhythmic wave-like contractions that move food
through GI tract
Functions of the GI Tract (2)
 Secretion:
 Includes both exocrine and endocrine secretions
oExocrine:
• HCl, H20, HC03-, bile, lipase, pepsin, amylase, trypsin,
elastase, and histamine are secreted into lumen of GI
tract
oEndocrine:
• Stomach and small intestine secrete hormones to
help regulate GI system
Gastrin, secretin, CCK, GIP, GLP-1, guanylin, VIP,
and somatostatin
Functions of the GI Tract (3)
 Digestion:
 Breakdown of food particles into subunits
(chemical structure change)
 Absorption:
 Process of passage of digestion (chemical subunits)
into blood or lymph
 Storage and elimination:
• Temporary storage and elimination of indigestible
food

Digestive System (GI Tract): Gross Anatomical
Arrangement
 GI tract divided into:
 Alimentary canal
 Accessory digestive
organs
 GI tract is 30 ft. long and

extends from mouth to anus
Marc Imhotep Cray, M.D. Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. 9
Layers of GI Tract
 Composed of 4 tunics:
• Mucosa
• Submucosa
• Muscularis
• Serosa
Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.

Mucosa
 Lines lumen of GI tract
 Consists of simple columnar epithelium
o Lamina propria:
• Thin layer of connective tissue containing
lymph nodules
o Muscularis mucosae:
• Thin layer of smooth muscle responsible for
folds
Folds increase surface area for absorption
o Goblet cells:
• Secrete mucus
Submucosa
 Thick, highly vascular layer of connective tissue
 Absorbed molecules enter blood and lymphatic

vessels
 Submucosal plexus (Meissner’s plexus):

 Provide autonomic nerve supply to muscularis
mucosae

Muscularis
 Responsible for segmental contractions and
peristaltic movement through GI tract
 Inner circular layer of smooth muscle
 Outer longitudinal layer of smooth muscle
o Contractions of these layers move food through tract
pulverize and mix food
 Myenteric plexus located between 2 muscle layers
 Major nerve supply to GI tract
o 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 GI Tract
 Extrinsic innervation:
 Parasympathetic nervous system (PNS):
oVagus and spinal nerves (preganglionic fibers):
• Stimulate motility and GI secretions
 Sympathetic nervous system(SNS):
oPostganglionic sympathetic fibers that pass through
submucosal and myenteric plexuses and innervate
GI tract:
• Reduce peristalsis and secretory activity

Regulation of the GI Tract (2)
 Enteric (Intrinsic) nervous system (ENS):
 Sites where parasympathetic fibers synapse with
postganglionic neurons that innervate smooth muscle
o Submucosal and myenteric plexuses:
• Local regulation of GI tract
Paracrine secretion:
 Molecules acting locally
 Hormonal secretion:
 Secreted by mucosa
From Mouth to Stomach
 Mastication (chewing):
 Mixes food with saliva which contains salivary amylase
oEnzyme that can catalyze partial digestion of starch
 Deglutition (swallowing):
 Begins as a voluntary activity Involves 3 phases:
oOral phase is voluntary
oPharyngeal and esophageal phases are involuntary
• Cannot be stopped
 Larynx is raised
 Epiglottis covers entrance to respiratory tract

From Mouth to Stomach cont.
 Involuntary muscular contractions and relaxations in
mouth, pharynx, larynx, and esophagus are
coordinated by swallowing center in medulla
 Esophagus:
• Connects pharynx to stomach
• Upper third contains skeletal muscle
• Middle third contains a mixture of skeletal and smooth
muscle
• Terminal (lower third) portion contains only smooth muscle

Esophagus
 Peristalsis:
 Produced by a series of localized
reflexes in response to distention of
wall by bolus
oWave-like muscular contractions:
• Circular smooth muscle contract
behind, relaxes in front of bolus
• Followed by longitudinal contraction

(shortening) of smooth muscle rate
of 2-4 cm/sec Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.
• After food passes into stomach, LES

constricts 19
Stomach
 Most distensible part of GI tract empties
into duodenum
 Functions of stomach:
 Stores food
 Initiates digestion of proteins
 Kills bacteria
 Moves food (chyme) into intestine

Stomach cont.
 Contractions of stomach churn chyme
 Mix chyme w gastric secretions
 Push food into intestine

Stomach cont.
Gastric mucosa has
gastric pits in folds
 Cells that line folds

deeper in mucosa are
gastric glands

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- Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.

HCl Production cont.
 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

Digestion and Absorption in Stomach
 Proteins partially digested by pepsin
 Carbohydrate digestion by salivary amylase is
soon inactivated by acidity
 Alcohol and aspirin are only commonly
ingested substances absorbed

Gastric and Peptic Ulcers
 Peptic ulcers:
• Erosions of mucous membranes of stomach or duodenum
produced by action of HCl
 Zollinger-Ellison syndrome:
• Ulcers of 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 mucosa
Covered w columnar epithelial

cells interspersed w goblet cells
Epithelial cells at tips of villi are

exfoliated and replaced by mitosis
in crypt of Lieberkuhn
Lamina propria contain

lymphocytes, capillaries, and
central lacteal Fox SI. Human Physiology 12th ed. New York, NY:
McGraw-Hill, 2011.
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 small intestine:
 Peristalsis: Insert fig. 18.14
o Slow movement
o Pressure at pyloric end of
small intestine is greater than
at distal end
 Segmentation:
o Major contractile activity of
small intestine
o Contraction of circular
smooth muscle
• Mix chyme Fox SI. Human Physiology 12th ed. New York, NY:
McGraw-Hill, 2011.
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
Fox SI. Human Physiology 12th ed. New York, NY:
McGraw-Hill, 2011.

Contractions of Intestinal Smooth Muscles
 When slow waves rise above threshold triggers APs by opening of VG
Ca2+ channels
 Inward flow of Ca2+:
o Produces upward depolarization phase
o Stimulates contraction of smooth muscle
 Repolarization:
 VG K+ channels open
o Slow waves decrease in amplitude as they are conducted.
 May stimulate contraction in proportion to magnitude of
depolarization
 Parasympathetic NS, stretch and gastrin increase amplitude of slow
waves
 Stimulate APs
 SNS decrease APs
Intestinal Smooth Muscle Action Potential
+30
Vg Ca++ Channel
-55 Vg K+ Channel
Fox SI. Human Physiology 12th ed. New York, NY:
McGraw-Hill, 2011.

Cells and Electrical Events in Muscularis

Large Intestine
 Outer surface bulges outward to form haustra
 Little absorptive function
o 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 H20, via active transport of NaCl into intestinal lumen
 Guanylin stimulates secretion of Cl- and H20, and inhibits absorption
of Na+ (minor pathway)
o Membrane contains Na+/K+ pumps
• Minor pathway

Fluid and Electrolyte Absorption in Intestine
 Small intestine:
 Most of fluid and electrolytes are absorbed by small
intestine
 Absorption of H20 occurs passively as a result of osmotic
gradient created by active transport
o Aldosterone stimulates NaCl and H20 absorption in ileum
 Large intestine:
 Absorbs about 90% of remaining volume
o 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 rectum
 Occurs when rectal pressure rises and external
anal sphincter relaxes
 Defecation reflex:
 Longitudinal rectal muscles contract to increase rectal
pressure
o Relaxation of internal anal sphincter
 Excretion is aided by contractions of abdominal and
pelvic skeletal muscles
o 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 (2)
Insert fig. 18.20

Hepatic Portal System
 Products of digestion that are absorbed are delivered
to liver
 Capillaries drain into 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 liver into bile ducts
 Can excrete these compounds
into intestine with bile

Major Categories of Liver Function

Bile Production and Secretion
 Liver produces and secretes 250–1500 ml of bile/day
 Bile pigment (bilirubin) is produced in spleen, bone marrow,
and liver
 Derivative of 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 hepatic vein
o Recycled, or filtered by kidneys and excreted in urine

Metabolism of Heme and Bilirubin
Bile Production and Secretion (2)
 Bile acids are derivatives of
cholesterol
 Major pathway of cholesterol
breakdown in body
 Principal bile acids are:
 Cholic acid
 Chenodeoxycholic acid
o Combine with glycine or taurine
to form bile salts Bile salts
aggregate as micelles
 95% of bile acids are absorbed by
ileum Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.

Detoxification of Blood
 Liver can remove hormones, drugs, and other
biologically active molecules from blood by:
 Excretion into the bile
 Phagocytosis by Kupffer cells
 Chemical alteration of the molecules
oAmmonia is produced by deamination of amino acids in
liver
oLiver converts it into urea
• Excreted in urine

Detoxification of the Blood cont.
 Inactivation of steroid hormones and drugs
 Conjugation of steroid hormones and xenobiotics
make them anionic
oCan 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 plasma globulins (except
immunoglobulins) are produced by liver
 Albumin:
 Constitutes 70% of total plasma protein
o Contributes most to colloid osmotic pressure in 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 inferior surface of
liver
 Stores and concentrates bile
 When gallbladder fills with bile, it expands
 Contraction of muscularis layer of gallbladder
ejects bile into common bile duct into duodenum
 When small intestine is empty, sphincter of
Oddi closes
 Bile is forced up to cystic duct to gallbladder
Pancreas
 Exocrine:
Acini:
oSecrete pancreatic juice
 Endocrine:
Islets of Langerhans:
oSecrete insulin and
glucagon

Pancreatic Juice
• Contains H20, HC03- 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. Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011.

Neural and Endocrine Regulation
Neural and endocrine mechanisms modify activity
of GI system
GI tract is both an endocrine gland, and a target for
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 1st 30 min. of a meal

Gastric Phase
 Arrival of food in stomach stimulates gastric phase
 Gastric secretion stimulated by:
oDistension
oChemical 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 secretion of HCl
oPositive feedback effect
• As more HCl and pepsinogen are secreted, more polypeptides
and amino acids are released
Gastric Phase cont.
 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
o D cells stimulate secretion
of somatostatin
Paracrine regulator to
inhibit secretion of gastrin
Marc Imhotep Cray, M.D. Fox SI. Human Physiology 12th ed. New York, NY: McGraw-Hill, 2011. 62
Intestinal Phase
 Inhibits gastric activity when chyme enters small
intestine
 Arrival of chyme increases osmolality and distension
 Activates sensory neurons of vagus and produces an
inhibitory neural reflex:
oInhibits gastric motility and secretion
oIn presence of fat, enterogasterone inhibits gastric motility
and secretion
 Hormone secretion:
 Inhibit gastric activity:
oSomatostatin, 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 cont.
Peristalsis:
 ACh and substance P
stimulate smooth muscle
contraction above bolus
 NO, VIP, and ATP stimulate
smooth muscle relaxation
below bolus

Paracrine Regulators of Intestine
 Serotonin (5-HT):
 Stimulates intrinsic afferents, which send impulses into
intrinsic nervous system; and activates motor neurons
 Motilin:
 Stimulates contraction of duodenum and stomach antrum.
 Guanylin:
 Activates guanylate cyclase, stimulating production of cGMP
o cGMP stimulates 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
rest of intestine
Secretion of Pancreatic Juice
 Secretion of pancreatic juice and bile is stimulated by:
 Secretin:
o Occurs in response to duodenal pH < 4.5
o Stimulates production of HC03- by pancreas
o Stimulates the liver to secrete HC03- into the bile
 CCK:
o Occurs in response to fat and protein content of chyme in
duodenum
o Stimulates production of pancreatic enzymes
o Enhances secretin
o Stimulates contraction of 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

Digestion and Absorption of Protein
 Digestion begins in stomach when pepsin digests
proteins to form polypeptides
 In duodenum and jejunum:
 Endopeptidases cleave peptide bonds in interior of
polypeptide:
o Trypsin
o Chymotrypsin
o Elastase
 Exopeptidases cleave peptide bonds from the ends of the
polypeptide:
o Carboxypeptidase
o Aminopeptidase
Digestion and Absorption of Protein cont.
 Free amino acids absorbed by
cotransport with Na+
 Dipeptides and tripeptides
transported by secondary active
transport using a H+ gradient to
transport them into cytoplasm
 Hydrolyzed into free amino acids
and then secreted into blood
Digestion and Absorption of Lipids
 Arrival of lipids in 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 monoglycerides
 Colipase coats the emulsification droplets and anchors
lipase enzyme to them
 Form micelles and move to brush border

Digestion and Absorption of Lipids cont.
 Free fatty acids, monoglycerides, and

lysolecithin leave micelles and enter into
epithelial cells
 Resynthesize triglycerides and phospholipids
within cell
oCombine 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
oLDLs transport cholesterol to organs and blood vessels
 HDLs transport excess cholesterol back to liver
Absorption of Fat

THE END

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Gastrointestinal Physiology-A Global Overview

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Gastrointestinal Physiology:

Prepared and presented by

nml stomach, gross nml stomach, endoscopy nml esophagus, micro

Marc Imhotep Cray, M.D. 4

Marc Imhotep Cray, M.D. 8

 GI tract is 30 ft. long and

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 Absorbed molecules enter blood and lymphatic

 Submucosal plexus (Meissner’s plexus):

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• Followed by longitudinal contraction

• After food passes into stomach, LES

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 Cells that line folds

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 Parietal cell’s basolateral

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 ACh and gastrin stimulate release of histamine

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Covered w columnar epithelial

Epithelial cells at tips of villi are

Lamina propria contain

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 Plates separated by sinusoids

 Contains phagocytic Kupffer cells

 Secretes bile into bile canaliculi which are drained

Insert fig. 18.20

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 Capillaries drain into hepatic portal vein, which carries

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Include preganglionic parasympathetic axons,

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