Biomedical Engineering Reference
In-Depth Information
(a)
(b)
To the heart and pulmonary circulation
Central vein
Inferior vena cava
From
hepatic artery
and portal vein
To gall bladder
and duodenum
Hepatic vein
Blood
Portal
triad
Hepatic lobules
Hepatic artery
Portal vein
Bile
Blood flow:
To hepatic vein and
inferior vena cava
1450 mL/min
To gall bladder and duodenum
(c)
A
B
Sinusoid (diameter 5-10 μm)
Hepatocyte plates
Space of disse
C
Bile canaliculi (diameter 0.5-1 μm)
Kupffer cell
Stellate cell
A
B
C
FIGURE 14.1 Structure of the liver. (a) The liver. The liver is perfused by the hepatic artery and portal vein.
Blood exits through the hepatic vein into the inferior vena cava, and bile drains into the gall bladder. (b) The
liver lobules. The liver parenchyma is composed of hexagonal lobules containing hepatocyte plates and the
sinusoids. The blood in each lobule comes from the portal vein and hepatic arteries; it drains out through
the central vein and into the inferior vena cava. (c) The liver sinusoid. Fenestrated hepatic sinusoids where
the arterial and portal veins merge. (From Wisse, E. et al. 2008. Gene Ther 15:1193-1199. With permission;
Adapted from Jacobs, F., Wisse, E. and De Geest, B. 2010. Am J Pathol 176:14 -21.)
(phagosomes) coalesce with intracellular organelles containing digestive proteins and an acidic
internal pH to mature into phagolysosomes and degrade the internalized colloid. The colloid is
then eliminated by exocytosis after degradation or sequestered in residual bodies within the cell if
it cannot be digested. Contacts between colloidal drug carriers (CDCs) and macrophages occur via
the recognition of opsonins on the CDC surface or through interactions with scavenger receptors on
Kupffer cells. The size and radius of the curvature of colloids highly influence both CDC-cell con-
tacts and internalizations (Harashima et al. 1994; Champion et al. 2008; Jiang et al. 2008). Because
Kupffer cells have a ruffled surface, privileged interactions and optimal phagocytosis occur when
the colloids have a diameter between 1 and 3 μm (Champion et  al. 2008; Doshi and Mitragotri
2010). Smaller particles offer less cooperative contacts with the cell membrane (Jiang et al. 2008),
and exploit other entry ways into cells (e.g., fluid phase pinocytosis or endocytosis) (Petros and
DeSimone 2010). Oppositely, larger particles cannot maximize contacts with the cell surface and
require extensive cytoskeleton remodeling to be internalized. In vitro , the upper size limit for
phagocytosis has been determined to be around 20 μm in diameter or with a volume at most 3 times
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