At the 18th day of gestation (2.5-mm stage), a thickening of
the ventral floor of the distal foregut, corresponding to the future
duodenum, heralds the appearance of the hepatic diverticulum. This
diverticulum is formed from the proliferation of endodermal cells
at the cranioventral junction of the yolk sac and foregut. Subsequently,
the hepatic diverticulum penetrates the adjacent mesoderm and capillary
plexus, known as the septum transversum. Cellular interactions between
the endoderm and mesoderm result in rapid cell proliferation and
the formation of hepatocytes, angioblasts, and sinusoids.1
By the third and fourth weeks of gestation (3- to 4-mm stage),
the growing diverticulum enlarges to form a double diverticulum
that projects into the septum transversum, then divides into a solid
cranial portion and hollow caudal portion is evident by the 5-mm stage.
The cranial portion differentiates into proliferating cords of hepatocytes
and intrahepatic bile ducts while the smaller caudal portion (pars
cystica) forms the primordium of the gallbladder, common bile duct,
and cystic duct.
The budding liver sequentially invades the vitelline veins and
then the umbilical (placental) veins. The vitelline veins run from
the gut–yolk sac complex to the heart. As the liver invades
the vitelline veins, the midsection of the veins becomes capillarized.
The caudal ends persist as the primitive portal veins, and the cranial
ends as the primitive hepatic veins. During the 6- to 7-mm stage
part of the left umbilical vein becomes the ductus venosus, which
shunts placenta derived arterial blood from the umbilical vein to
the inferior vena cava. After birth the obliterated prehepatic segments
of the umbilical veins atrophy to become the round ligament and
the ductus venosus becomes the ligamentum venosum.
The hepatocytes of the hepatic portion grow as thick epithelial
sheets intermingling between branching channels of the vitelline veins
within the septum transversum to form a system of connecting liver
cell plates, and the capillaries become the hepatic sinusoids. The
sinusoids, present by 5 weeks of gestation, act as templates for
the three-dimensional growth of the hepatic cords. The liver cell
plates are initially 3 to 5 cells thick. However, over time they
gradually transform to one-cell-thick plates, a process that is
not complete until 5 years of age. Intrahepatic bile ducts begin
to form at 6 weeks of gestation within the hilum of the liver and
gradually spread to the periphery until complete at 3 months.
The pars cystica is initially hollow, but epithelial proliferation
obliterates the lumen early in its development. Therefore, both
the primitive gallbladder and common bile duct consist of solid
chords of epithelial cells directly beneath the developing liver
in the 6- to 7-mm embryo. Recanalization of the common bile duct
and hepatic duct occurs in the 7- to 8-mm and 10-mm embryo, respectively.
At the 16-mm stage the proximal gallbladder and cystic duct are
hollow. At the third month the gallbladder is fully hollow, and
the intrahepatic and ...