13.15). This outgrowth, the hepatic diverticulum, or liver bud, consists of rapidly proliferating cells that penetrate the septum transversum, that is, the mesodermal plate between the pericardial cavity and the stalk of the yolk sac (Figs. 13.14 and 13.15). While hepatic cells continue to penetrate the septum, the connection between the hepatic diverticulum and the foregut (duodenum) narrows, forming the bile duct. A small ventral outgrowth is formed by the bile duct, and this outgrowth gives rise to the gallbladder and the cystic duct (Figs. 13.15). During further development, epithelial liver cords intermingle with the vitelline and umbilical veins, which form hepatic sinusoids. Liver cords differentiate into the parenchyma (liver cells) and form the lining of the biliary ducts. Hematopoietic cells, Kupffer cells, and connective tissue cells are derived from mesoderm of the septum transversum.
When liver cells have invaded the entire septum transversum, so that the organ bulges caudally into the abdominal cavity, mesoderm of the septum transversum lying between the liver and the foregut and the liver and ventral abdominal wall becomes membranous, forming the lesser omentum and falciform ligament, respectively Together, having formed the peritoneal connection between the foregut and the ventral abdominal wall, they are known as the ventral mesogastrium (Fig. 13.15).
Mesoderm on the surface of the liver differentiates into visceral peritoneum except on its cranial surface (Fig. 13.15B). In this region, the liver remains in contact with the rest of the original septum transversum. This portion of the septum, which consists of densely packed mesoderm, will form the central tendon of the diaphragm. The surface of the liver that is in contact with the future diaphragm is never covered by peritoneum; it is the bare area of the liver (Fig. 13.15).
In the 10th week of development the weight of the liver is approximately 10% of the total body weight. Although this may be attributed partly to the large numbers of sinusoids, another important factor is its hematopoietic function. Large nests of proliferating cells, which produce red and white blood cells, lie between hepatic cells and walls of the vessels. This activity gradually subsides during the last 2 months of intrauterine life, and only small hematopoietic islands remain at birth. The weight of the liver is then only 5% of the total body weight.
Another important function of the liver begins at approximately the 12th week, when bile is formed by hepatic cells. Meanwhile, since the gallbladder and cystic duct have developed and the cystic duct has joined the hepatic duct to form the bile duct (Fig. 13.15), bile can enter the gastrointestinal tract. As a result, its contents take on a dark green color. Because of positional changes of the duodenum, the entrance of the bile duct gradually shifts from its initial anterior position to a posterior one, and consequently, the bile duct passes behind the duodenum (see Figs. 13.21 and 13.22).
All of the foregut endoderm has the potential to express liver-specific genes and to differentiate into liver tissue. However, this expression is blocked by factors produced by surrounding tissues, including ectoderm, non-cardiac mesoderm, and particularly the notochord (Fig. 13.19). The action of these inhibitors is blocked in the prospective hepatic region by fibroblast growth factors (FGFs)
Figure 13.19 Diagrams of the cardiac and hepatic forming regions illustrating induction of liver development. All of the gut endoderm has the potential to form liver tissue, but this capacity is repressed by inhibitors secreted by neighboring mesoderm, ectoderm, and the notochord. Stimulation of hepatic development is achieved by secretion of fibroblast growth factor (FGF) by cardiac mesoderm that inhibits activity of the inhibitors, thereby specifying the hepatic field and initiating liver development. This interaction demonstrates that not all inductive processes are a result of direct signaling by an inducing molecule, but instead may occur by removal of a repressor signal.
secreted by cardiac mesoderm. Thus, the cardiac mesoderm "instructs" gut endoderm to express liver specific genes by inhibiting an inhibitory factor of these same genes. Once this "instruction" is received, cells in the liver field differentiate into both hepatocytes and biliary cell lineages, a process that is at least partially regulated by hepatocyte nuclear transcription factors (HNF3 and 4).
CLINICAL CORRELATES Liver and Gallbladder Abnormalities
Variations in liver lobulation are common but not clinically significant, Accessory hepatic ducts and duplication of the gallbladder (Fig. 13.20) are also common and usually asymptomatic. However, they become clinically important under pathological conditions. In some cases the ducts, which pass through a solid phase in their development, fail to recanalize (Fig. 13.20). This defect, extrahepatic biliary atresia, occurs in 1/15,000 live births. Among hsijauc duct gfe ¿up, ca—irated hsijauc duct gfe ¿up, ca—irated
Duplüalion c/i giillblndiJ^r
Duplüalion c/i giillblndiJ^r
Figure 13.20 A. Obliteration of the bile duct resulting in distention of the gallbladder and hepatic ducts distal to the obliteration. B. Duplication of the gallbladder.
n.innrr-ilic t'jif gt;i>ViCh
n.innrr-ilic t'jif hepallc ddet
Figure 13.21 Stages in development of the pancreas. A. 30 days (approximately 5 mm). B. 35 days (approximately 7 mm). Initially the ventral pancreatic bud lies close to the liver bud, but later it moves posteriorly around the duodenum toward the dorsal pancreatic bud.
patients with extrahepatic biliary atresia, 15 to 20% have patent proximal ducts and a correctable defect, but the remainder usually die unless they receive a liver transplant. Another problem with duct formation lies within the liver itself; it is intrahepatic biliary duct atresia and hypoplasia. This rare abnormality (1/100,000 live births) may be caused by fetal infections. It may be lethal but usually runs an extended benign course.
Was this article helpful?