The anlage of the biliary ducts and liver consists of a diverticulum that appears on the ventral aspect of the foregut in 3 mm embryos around the 4th week of embryonic development. The cranial portion becomes the liver; a caudal bud forms the ventral pancreas; and an intermediate bud develops into the gallbladder.
Originally hollow, the hepatic diverticulum becomes a solid mass of cells that later recanalizes to form the ducts. The smallest ducts—the bile canaliculi—first appear as a basal network between the primitive hepatocytes that eventually expands throughout the liver.
The hepatic diverticulum divides into two parts:
Cranial portion (larger): forms the liver primordium.
Caudal portion (smaller): forms the gallbladder and cystic duct.
The stalk of the hepatic diverticulum becomes the common bile duct (CBD).
The cranial portion grows rapidly into the septum transversum mesenchyme (future diaphragm and ventral mesentery).
Endodermal cells differentiate into:
Hepatoblasts → become hepatocytes and intrahepatic bile ducts.
Bipotential cells → give rise to cholangiocytes (bile duct epithelium).
Mesoderm of the septum transversum contributes to:
Kupffer cells (liver macrophages).
Stellate (Ito) cells.
Connective tissue and hematopoietic cells.
By the 6th week, the liver is a major site of hematopoiesis, giving the embryo a large abdominal prominence.
Later, liver hematopoiesis declines as the bone marrow takes over, and hepatocyte function (e.g., bile secretion) begins.
Intrahepatic bile ducts form by remodeling of hepatoblast cords into ductal plates around the portal vein, then differentiating into mature ducts.
Extrahepatic bile ducts (hepatic ducts, cystic duct, CBD) arise from the stalk of the hepatic diverticulum.
The gallbladder primordium undergoes vacuolization, creating a lumen.
Bile secretion begins by the 12th week of gestation.
Bile pigments are released into the duodenum → give meconium its greenish color.
Biliary atresia: failure of bile ducts to canalize or abnormal remodeling → obstructive jaundice in newborns.
Choledochal cysts: congenital dilatations of bile ducts.
Accessory hepatic ducts or gallbladders: due to abnormal budding.
✅ Summary:
The liver and biliary system originate from the foregut endoderm as the hepatic diverticulum. The cranial part forms the liver, the caudal part forms the gallbladder and cystic duct, and the stalk becomes the common bile duct. Hepatoblasts form hepatocytes and bile ducts, while mesodermal cells contribute Kupffer and connective tissue elements. By week 12, bile secretion begins.
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