Architecture of the Liver
The liver is the largest gland in the body and performs an astonishingly large
number of tasks that impact all body systems. One consequence of this
complexity is that hepatic disease has widespread effects on virtually all
other organ systems. At the risk of losing site of the forest by focusing on the
trees, we will focus on three fundamental roles of the liver:

Vascular functions, including formation of lymph and
the hepatic phagocytic system.

Metabolic achievements in control of synthesis and
utilization of carbohydrates, lipids and proteins.

Secretory and excretory functions, particularly with
respect to the synthesis of secretion of bile.
The latter is the only one of the three that directly affects digestion - the
liver, through its biliary tract, secretes bile acids into the small intestine
where they assume a critical role in the digestion and absorption of dietary
lipids. However, understanding the vascular and metabolic functions of the
liver is critical to appreciating the gland as a whole.
Architecture of the Liver and Biliary Tract
The liver lies in the
abdominal cavity, in
contact with diaphragm.
As seen in image to the
right of a mouse liver, its
mass is divided into
several lobes, the number
and size of which vary
among species. In most
mammals, a greenish sac
- the gall bladder - is seen
attached to the liver and
careful examination will
reveal the common bile
duct, which delivers bile
from the liver and gall
bladder into the
duodenum.
Understanding function
and dysfunction of the
liver, more than most
other organs, depends on understanding its structure. The major aspects of hepatic structure that require
detailed attention include:

The hepatic vascular system, which has several unique characteristics relative to
other organs.

The biliary tree, which is a system of ducts that transports bile out of the liver into the
small intestine.

The three dimensional arrangements of the liver cells, or hepatocytes and their
association with the vascular and biliary systems.
The Hepatic Vascular System
The circulatory system of the liver is unlike that seen in any other organ. Of great importance is
the fact that a majority of the liver's blood supply is venous blood! The pattern of blood flow in the
liver can be summarized as follows:

Roughly 75% of the blood entering the liver is venous blood from the portal vein.
Importantly, all of the venous blood returning from the small intestine, stomach,
pancreas and spleen converges into the portal vein. One consequence of this is that
the liver gets "first pickings" of everything absorbed in the small intestine, which, as we
will see, is where virtually all nutrients are absorbed.

The remaining 25% of the blood supply to the liver is arterial blood from the
hepatic artery.

Terminal branches of the hepatic portal vein and hepatic artery empty together
and mix as they enter sinusoids in the liver. Sinusoids are distensible vascular
channels lined with highly fenestrated or "holey" endothelial cells and bounded
circumferentially by hepatocytes. As blood flows through the sinusoids, a considerable
amount of plasma is filtered into the space between endothelium and hepatocytes (the
"space of Disse"), providing a major fraction of the body's lymph.

Blood flows through the sinusoids and empties into the central vein of each
lobule.

Central veins coalesce into hepatic veins, which leave the liver and empty into
the vena cava.
The Biliary System
The biliary system is a series of channels and ducts that conveys bile - a secretory and excretory
product of hepatocytes - from the liver into the lumen of the small intestine. Hepatocytes are
arranged in "plates" with their apical surfaces facing and surrounding the sinusoids. The basal faces of
adjoining hepatocytes are welded together by junctional complexes to form canaliculi, the first channel
in the biliary system. A bile canaliculus is not a duct, but rather, the dilated intercellular space
between adjacent hepatocytes.
Hepatocytes secrete bile into the canaliculi, and those secretions flow parallel to the sinusoids, but in
the opposite direction that blood flows. At the ends of the canaliculi, bile flows into bile ducts, which
are true ducts lined with epithelial cells. Bile ducts thus begin in very close proximity to the terminal
branches of the portal vein and hepatic artery, and this group of structures is an easily recognized and
important landmark seen in histologic sections of liver - the grouping of bile duct, hepatic arteriole
and portal venule is called a portal triad.
Small bile ducts, or ductules, anastomose into larger and larger ducts, eventually forming the
common bile duct, which dumps bile into the duodenum. A sphincter known as the sphincter of
Oddi is present around the common bile duct as it enters the intestine.
The gall bladder is another important structure in the biliary system of many species. This is a
sac-like structure adhering to the liver which has a duct (cystic duct) that leads directly into the common
bile duct. During periods of time when bile is not flowing into the intestine, it is diverted into the
gall bladder, where it is dehydrated and stored until needed.
Architecture of the Hepatic Parenchyma
The liver is covered with a connective tissue capsule that branches and extends throughout the
substance of the liver as septae. This connective tissue tree provides a scaffolding of support and the
highway which along which afferent blood vessels, lymphatic vessels and bile ducts traverse the liver.
Additionally, the sheets of connective tissue divide the parenchyma of the liver into very small units
called lobules.
The hepatic lobule is the structural unit of the liver. It consists of a roughly hexagonal arrangement
of plates of hepatocytes radiating outward from a central vein in the center. At the vertices of the lobule
are regularly distributed portal triads, containing a bile duct and a terminal branch of the hepatic artery
and portal vein. Lobules are particularly easy to see in pig liver because in that species they are well
delineated by connective tissue septae that invaginate from the capsule.
Additional information on liver structure is presented in the sections on hepatic histology.
Physiology of the Hepatic Vascular System
Hepatic Blood Volume and Reservoir Function
The liver receives approximately 30% of resting cardiac output and is therefore a very vascular
organ. The hepatic vascular system is dynamic, meaning that it has considerable ability to both store
and release blood - it functions as a reservoir within the general circulation.
In the normal situation, 10-15% of the total blood volume is in the liver, with roughly 60% of that in
the sinusoids. When blood is lost, the liver dynamically adjusts its blood volume and can eject
enough blood to compensate for a moderate amount of hemorrhage. Conversely, when vascular
volume is acutely increased, as when fluids are rapidly infused, the hepatic blood volume expands,
providing a buffer against acute increases in systemic blood volume.
Formation of Lymph in the Liver
Approximately half of the lymph formed in the body is formed in the liver. Due to the large pores or
fenestrations in sinusoidal endothelial cells, fluid and proteins in blood flow freely into the space
between the endothelium and hepatocytes (the "space of Disse"), forming lymph. Lymph flows
through the space of Disse to collect in small lymphatic capillaries associated with portal triads (the
reason they are not called portal tetrads is because these lymphatic vessels are virtually impossible to
identify in standard histologic sections), and from there in the systemic lymphatic system.
As you might expect, if pressure in the sinusoids increases much above normal, there is a
corresponding increase in the rate of lymph production. In severe cases the liver literally
sweats lymph, which accumulates in the abdominal cavity as ascitic fluid. What lesions can
you envision that would raise blood pressure in sinusoids, resulting in production of
ascites?
The Hepatic Phagocytic System
The liver is host to a very important part of the phagocytic system. Lurking in the sinusoids are large
numbers of a type of tissue macrophage known as the Kupffer cell.
Kuppfer cells are actively phagocytic and represent the main cellular system for removal of
particulate materials and microbes from the circulation. Their location just downstream from
the portal vein allows Kupffer cells to efficiently scavenge bacteria that get into portal
venous blood through breaks in the intestinal epithelium, thus preventing invasion of the
systemic circulation.