
and the head of the pancreas before it enters the
duodenum.
Fine Structure
0004 At the tissue level, the liver is comprised of a large
series of channels lined with endothelial cells, the
sinusoids, which run between layers or plates of hepa-
tocytes. The endothelial cells possess fenestrations,
which allow access of circulating blood to the sinus-
oidal surface of the hepatocytes. Some of the cells
lining the sinusoids, Kuppfer cells, possess phagocytic
activity. The space of Disse, i.e., the space between the
endothelial cells and the hepatocytes, contains inter-
stitial fluid. The membrane transport of nutrients and
waste material between the space of Disse and the
parenchymal cells is facilitated by the numerous
microvilli, which extend the sinusoidal surface of
these cells. From and around the liver branches of
the hepatic artery, portal vein and bile duct are
carried portal tracts, the smallest of which contain
terminal branches supplying groups of sinusoids that
form a functional unit, the acinus. Blood from each
acinus passes into a number of efferent veins. It is
the radially orientated sinusoids centered on these
efferent veins that give the liver its classical lobular
architecture.
0005 Histochemical studies have demonstrated a marked
heterogeneity of hepatocytes, with cells at different
locations differing both structurally and functionally.
This differentiation probably reflects the many spe-
cific metabolic functions that the liver has to meet.
The overall functional capacity of the liver (liver func-
tional mass) is highly dependent on the number and
activity of these hepatocytes and their contact with
circulating blood (effective liver perfusion).
Functions of the Liver
0006 The anatomical site and cellular architecture of the
liver enable it to perform many diverse metabolic
functions that are essential to the body. Its position,
between the digestive tract and the general circula-
tion, ensures that substances ingested orally and
absorbed by the intestine must normally pass to the
liver. As a result, the liver has developed the ability
not only to receive, process, and store these sub-
stances but also to release them or their metabolites
in a highly regulated fashion by monitoring demand
and responding to multiple hormonal and neural
stimuli.
0007 A cardinal role of the liver is to regulate the
supply and utilization of energy-containing substrates
through its participation in the integrated control of
carbohydrate, protein, and lipid metabolism. In the
body, there is a fine balance between anabolic and
catabolic processes, between supply and demand.
This state of metabolic homeostasis is essential for
the maintenance of an adequate and continual supply
of fuel to the tissues, especially cerebral tissue, as the
body adapts to periods of relative plenty alternating
with periods of fasting. This is facilitated by three
processes: providing fuel from ingested food to meet
immediate energy demands; storing fuel reserve as
glycogen in the liver and muscle, at the same time
replenishing tissue protein lost since the last meal;
diverting excess energy-rich substrate into triglycer-
ide for transport to adipose tissue for storage. As for
any tissue, these metabolic processes in the liver are
dependent on several factors, including the circulat-
ing concentration of substrate, blood flow to tissue,
cell permeability, the mechanism of entry to the
metabolic pathways and their hormonal regulation.
(See Amino Acids: Metabolism; Carbohydrates:
Digestion, Absorption and Metabolism; Fatty Acids:
Metabolism; Glycogen.)
0008The liver is the major site of plasma protein synthe-
sis, including albumin, the a-andb-globulins, clotting
factors, and transport proteins. These proteins have
important roles in body homeostasis: regulation of
blood coagulation and hemostasis; the transport and
optimization of circulating concentrations of calcium
and magnesium ions, bilirubin, fatty acids, and hor-
mones. Also, albumin contributes to the maintenance
of the plasma colloidal oncotic pressure and hence the
control of body fluid distribution. There is a close
relationship between the liver, gut, and muscles with
respect to amino acid metabolism. The average adult
turns over about 2% of total body protein, approxi-
mately 250 g per day, with muscle the major source,
contributing 140 g, and dietary intake accounting for
90 g. After a meal, approximately 25% of the amino
acid nitrogen absorbed into the portal bloodstream
reaches peripheral tissues because the liver has the
ability to regulate the rate of gluconeogenesis and
transamination, thereby modifying the circulating
plasma amino acid composition. The aromatic
amino acids phenyalanine, tyrosine, and methionine
are preferentially metabolized to urea, while the
branched-chain amino acids valine, leucine, and iso-
leucine are selectively able to reach peripheral muscle
for reincorporation into protein. A major synthetic
function of the liver is the formation of bile acids
from cholesterol and their secretion into the intestine,
thereby generating bile flow and facilitating dietary
fat emulsification and absorption. (See Bile.)
0009Substances circulating in the systemic bloodstream
have access to the liver by way of the hepatic artery
and the mesenteric artery. The liver is the main site
of metabolic transformation and detoxification of
3594 LIVER/Structure and Function