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M3 sem 1 case 7:

Liver Microstructure
COMMONWEALTH OF AUSTRALIA
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Presenter:
Dr Julie Haynes, Anatomy & Pathology, room N127,
Medical School.
Phone: 8313 5769, email: julie.haynes@adelaide.edu.au
J Haynes 2006
Human liver has minimal CT & lobulation is indistinct.
M3 sem 1 case 7, Image 1 - Liver Lobulation
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J Haynes 2006
The micrograph shows that pig liver has more connective tissue than
human liver and shows the arrangement of hepatocytes into classical
lobules. All blood flowing from the edge of the lobule drains into the
central vein. Centrals veins sublobular veins hepatic veins inferior
vena cava.
M3 sem 1 case 7, Image 2 - Liver Lobulation
The hexagonal classical
liver lobule:

hexagon plates of cells

central vein with radiating
strands of hepatocytes,
separated by sinusoids.

portal triads in corners of
hexagon; consist of hepatic
artery, hepatic portal vein &
bile duct

Classical lobule based on
blood drainage of the liver.

J Haynes 2006
M3 sem 1 case 7, Image 3 - Liver Lobulation
portal triad
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Fawcett DW. Concise Histology, Chapman and Hall, New York, 1997
The classical lobule
- considers the drainage of blood
M3 sem 1 case 7, Image 4 - Liver Lobulation
The liver acinus
(or functional unit)
- considers the
blood supply
hepatic acinus
Considers blood supply.
diamond shaped,

zone 1 (perilobular)
cells have have first access
to oxygen and nutrients in
the blood ;

zone 2 (mid zone)
cells are less favoured;

zone 3 (centrilobular)
cells are least favoured

Cells in zone 3 are most
vulnerable to damage from
hypoxia, poor perfusion and
certain toxins (eg. alcohol)
whereas cells in zone 1 are
affected least.
Fawcett DW. Concise Histology, Chapman and Hall, New York, 1997
M3 sem 1 case 7, Image 5 - Liver Lobulation
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Blood flow in classical
lobule (blue)
At portal triads, blood in
branches of hepatic portal
vein &hepatic artery enter
sinusoids.
Flows to central veins that
empty into sublobular
veins, hepatic veins & then
inferior vena cava.

Bile flow in classical
lobule (green)
Canaliculi, small gaps
between hepatocytes,
drain bile to periphery of
lobules into the smallest
epithelial lined bile ducts at
the portal triads
Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005
M3 sem 1 case 7, Image 6 - Liver Lobulation
M3 sem 1 case 7, Image 7 - Liver
In the medium power view of the liver (pig) identify D, E, & F. What
label is the closest to cells in zone 3 of the liver acinus?
F
D
E
E
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M3 sem 1 case 7, Image 8 - Liver
In the high power view of the liver: From what adjoining structure(s) has the fluid
in H come? From what adjoining structure(s) has the fluid in I come? From what
adjoining structure(s) has the fluid in J come? From what adjoining structure(s)
has the fluid in K come?
H
H
H
H
H
I
I
J
K
M3 sem 1 case 7, Image 9A - Liver
The HP micrograph shows sinusoids and hepatocytes. Sinusoids are wide tortuous blood channels that
allow maximum exchange between blood & hepatocytes. They are incompletely lined by endothelial cells
& phagocytic cells (Kupffer cells). Space of Disse (not seen in routine sections of normal liver) is present
between sinusoids and hepatocytes and is where the actual exchange between hepatocytes and blood
occurs. Bile canaliculi are also not shown in routine sections. Hepatocytes are large cells (compare size
with RBCs); vesicular nucleus indicates active protein production and patchy cytoplasmic staining (not
shown in this photo) is due to abundant glycogen. Lipid appears as round clear droplets in hepatocytes.
Kupffer
cell?
endothelial
cell
B
lipid
endothelial cell
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M3 sem 1 case 7, Image 9B - Liver
The HP micrograph shows sinusoids and hepatocytes. Hepatocytes are large
cells (compare size with RBCs); vesicular nucleus indicates active protein
production and patchy cytoplasmic staining is due to abundant glycogen.
J Haynes 2006
J Haynes 2006
M3 sem 1 case 7, Image 9C - Liver Sinusoids
The HP view shows Kupffer cells stained bright pink.
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M3 sem 1 case 7, Image 10 - Liver Sinusoids
The electron micrograph shows (1) Kupffer cell, lining a sinusoid &
(2) Ito cell in space of Disse
Kupffer cell Ito cell
sinusoid
microvilli of hepatocyte in space of Disse
Ross, MH, & Pawlina, W. Histology, 5 ed, Lippincott, Williams & Wilkins, Baltimore, 2006.
sinusoid
J Haynes 2006
M3 sem 1 case 7, Image 11 Bile Canaliculi
The high power micrograph shows bile canaliculi, stained by a special technique
to show alkaline phosphatase. Canaliculi are in between hepatocytes and the bile
in them drains to bile ducts at the periphery of the classical lobules.
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The top LM drawing shows how
the intercellular spaces connect
together to form a drainage
system that flows into the
epithelial lined bile ducts in the
portal triads.

The bottom EM drawing shows
the ultrastructure of hepatocytes.
Note the Space of Disse where
exchange between hepatocytes
and blood takes place and the
small intercellular spaces,
canaliculi, where bile is
secreted.
sinusoid
Kupffer cell
endothelial cell
space of Disse
Ito cell
Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005
M3 sem 1 case 7, Image
12 Bile Canaliculi
bile canaliculus
M3 sem 1 case 7, Image 13 - Liver
The HP micrograph shows a portal triad. Identify the triad components A, B,
and C. What would be present in abundance in cell D but not cell E?
B
C C
A
cell E
cell D
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M3 sem 1 case 7, Image
14A Hepatocyte
Structure and Function
many organelles
much synthesis
high energy requirements
each cell has multiple
biochemical activities
many enzymes in SER &
RER are part of metabolic
pathways
e.g. alanine aminotransferase
(ALT) Catalyses transfer of
amino group from analine to
alpha-ketoglutamate, to form
pyruvate & glutamate.
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M3 sem 1 case 7, Image 14B Glycogen Storage
Carbohydrate storage in the
liver. Glycogen storage is
associated with the smooth
endoplasmic reticulum (SER).
When glucose is needed,
glycogen is degraded. In
several diseases, glycogen
degradation is depressed,
resulting in abnormal
intracellular accumulations of
glycogen.
Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005
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M3 sem 1 case 7, Image 14C Protein Production in
Hepatocytes
Proteins produced by hepatocytes
are synthesized in the RER,
modified and packaged in
Golgi complex, secreted by
exocytosis.

The impairment of protein
synthesis in liver diseases and
starvation leads to several
complications, since most of
these proteins are carriers,
important for the bloods
osmotic pressure and for
coagulation e.g. albumin,
fibrinogen, and prothrombin

Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005
M3 sem 1 case 7, Image 14D Bile Acids Secretion
Mechanism of secretion of bile
acids.
About 90% of bile acids are
reabsorbed in the intestine and
transported to the liver to be
recycled.
The remaining 10% are
synthesized in the liver by the
conjugation of cholic acid with the
amino acids glycine and taurine.
This process occurs in the smooth
endoplasmic reticulum (SER).

Alkaline phosphatase is bound to
canaliculi membrane and is
cleaved by bile acids during
secretion. In bile obstruction AP
enters the blood.

Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005
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M3 sem 1 case 7, Image 14E
Bilirubin Secretion
Water-insoluble bilirubin from hemoglobin
degradation in macrophages is tightly
bound with albumin in transport in the
blood.
Glucuronyltransferase in the SER of
hepatocytes conjugates bilirubin with
glucuronic acid to form water-soluble
bilirubin glucuronide. It is then secreted
into canaliculi.
When bile secretion is blocked, the yellow
bilirubin or bilirubin glucuronide is not
excreted; it accumulates in the blood,
and jaundice results.
More common cause of jaundice is the
obstruction of bile flow as a result of
gallstones or tumours of the pancreas.

Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005
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Junqueira, LC & Carneiro, J. Basic Histology, 11 ed, McGraw Hill, New York, 2005
The diagram shows a different focus of functions for hepatocytes relating to their location in
the liver acinus. After eating, cells in zone I are the first to take up glucose and store it as
glycogen. They are also the first to release glucose back into the blood after fasting. Cells in
zone II and zone III have progressively less access to glucose and oxygen. Cells in zone III
have more enzymes associated with anaerobic activities (e.g. glycolysis).
M3 sem 1 case 7, Image 15 Hepatocyte Function
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M3 sem 1 case 7: Answers

M3 sem 1 case 7, Image 7 Ans: D = central vein, E = sinusoids, F = hepatic portal
vein (branch). Label D is closest to cells in zone 3.

M3 sem 1 case 7, Image 8 Ans: H: from hepatic artery and hepatic portal vein; I: from
canaliculi; J: from hepatic artery; K: from hepatic portal vein.

M3 sem 1 case 7, Image 13 Ans: A = bile duct tributary ; B = branch of hepatic portal
vein; C = branch of hepatic artery. Cells D contain glycogen..