19.4 Hepatobiliary Excretion of Nanoparticles
19.4.1 Anatomy and Physiology of the Liver
The liver is the biggest solid organ weighing 1.5–2.0 kg on average in the human
adult. The liver can be found just below the right side diaphragm and partially
covered by rib cage [47]. The liver consists of the larger right and the smaller left
lobes which are separated by the hepatic vein in the middle. The primary functions
of the liver include: (1) regulation of the glucose and fat metabolism, (2) production
and secretion of bile, (3) metabolism of drugs, chemicals, and alcohol (4) production of essential body proteins including albumin, coagulation factors (5) regulation
of hormone balances including sex, thyroid hormones, and cortisone. The liver
consists of functional groups of hepatic lobules. The lobules are composed of plates
of hepatocytes radiating from a central vein and form roughly hexagonal shapes.
The central vein drains into hepatic vein. At the each corner of the lobule, porta
triads run vertically. The porta triads was named because there are branches of the
hepatic artery, hepatic portal vein, bile duct, but currently, it has been revealed that
there is two more components in the porta triads, which are a lymphatic vessel and
the vagus nerve.
Inside the hepatic lobules, there are multiple radial arrays of hepatocytes and
sinusoids. The sinusoid is a type of capillary system which has fenestrated
endothelium. The sinusoid receives blood from both oxygen-rich hepatic artery and
nutrient-rich portal vein. The blood is mixed in the sinusoids and drains into hepatic
vein. Hepatocytes are located beside the sinusoids with gaps named space of Disse
while Kupffer cell resides inside of the sinusoid. However, hepatocytes can interact
with materials in the sinusoid though fenestration in the sinusoids. Between the
hepatocytes, biliary canaliculus can be found which consists of biliary epithelial
cells. Bile in the biliary canaliculi drains into larger bile ducts in the porta triad and
further collected through the biliary tree (Fig. 19.8) [48]. Bile can be directly
secreted into the duodenum via extrahepatic bile duct or accumulated in the gall
bladder and secreted into duodenum when the gall bladder squeezes. Sixty to eighty
percent of the cells in the liver are hepatocytes and the other twenty to forty percent
of the cells include Kupffer cells, sinusoidal endothelial cells, stellate cells, biliary
epithelial cells, lymphocytes and circulating blood cells [49].
19.4.2 Hepatobiliary Excretion
Not all NPs in the liver are captured in the MPS. Although the hepatocytes are
separated from the sinusoid, the capillary system in the liver, some NPs can make
their way to the hepatocytes. To be excreted via the hepatobiliary pathway, size of
NPs should be smaller than 120–150 nm which is the size of hepatic sinusoidal
fenestration. In 1989, Renaud et al. reported that low-density lipoprotein
19 Excretion and Clearance
359
19.4.1 Anatomy and Physiology of the Liver
The liver is the biggest solid organ weighing 1.5–2.0 kg on average in the human
adult. The liver can be found just below the right side diaphragm and partially
covered by rib cage [47]. The liver consists of the larger right and the smaller left
lobes which are separated by the hepatic vein in the middle. The primary functions
of the liver include: (1) regulation of the glucose and fat metabolism, (2) production
and secretion of bile, (3) metabolism of drugs, chemicals, and alcohol (4) production of essential body proteins including albumin, coagulation factors (5) regulation
of hormone balances including sex, thyroid hormones, and cortisone. The liver
consists of functional groups of hepatic lobules. The lobules are composed of plates
of hepatocytes radiating from a central vein and form roughly hexagonal shapes.
The central vein drains into hepatic vein. At the each corner of the lobule, porta
triads run vertically. The porta triads was named because there are branches of the
hepatic artery, hepatic portal vein, bile duct, but currently, it has been revealed that
there is two more components in the porta triads, which are a lymphatic vessel and
the vagus nerve.
Inside the hepatic lobules, there are multiple radial arrays of hepatocytes and
sinusoids. The sinusoid is a type of capillary system which has fenestrated
endothelium. The sinusoid receives blood from both oxygen-rich hepatic artery and
nutrient-rich portal vein. The blood is mixed in the sinusoids and drains into hepatic
vein. Hepatocytes are located beside the sinusoids with gaps named space of Disse
while Kupffer cell resides inside of the sinusoid. However, hepatocytes can interact
with materials in the sinusoid though fenestration in the sinusoids. Between the
hepatocytes, biliary canaliculus can be found which consists of biliary epithelial
cells. Bile in the biliary canaliculi drains into larger bile ducts in the porta triad and
further collected through the biliary tree (Fig. 19.8) [48]. Bile can be directly
secreted into the duodenum via extrahepatic bile duct or accumulated in the gall
bladder and secreted into duodenum when the gall bladder squeezes. Sixty to eighty
percent of the cells in the liver are hepatocytes and the other twenty to forty percent
of the cells include Kupffer cells, sinusoidal endothelial cells, stellate cells, biliary
epithelial cells, lymphocytes and circulating blood cells [49].
19.4.2 Hepatobiliary Excretion
Not all NPs in the liver are captured in the MPS. Although the hepatocytes are
separated from the sinusoid, the capillary system in the liver, some NPs can make
their way to the hepatocytes. To be excreted via the hepatobiliary pathway, size of
NPs should be smaller than 120–150 nm which is the size of hepatic sinusoidal
fenestration. In 1989, Renaud et al. reported that low-density lipoprotein
19 Excretion and Clearance
359