Formation of the liver and biliary tract during embryogenesis

The liver with its duct system and gall bladder develop from the hepatic diverticulum of the ventral endoderm of the primary midgut. Liver development begins in the 4th week of the intrauterine period. The future bile ducts are formed from the proximal part of the diverticulum, and the hepatic beams from the distal part.

Rapidly multiplying endodermal cells of the cranial part (pars hepatica) are introduced into the mesenchyme of the abdominal mesentery. As the hepatic diverticulum grows, the mesothermal sheets of the abdominal mesentery form a connective tissue capsule of the liver with its mesothelial cover and interlobular connective tissue, as well as smooth muscles and the framework of the liver ducts. In the 6th week, the lumens of the liver beams - "bile capillaries" - become visible. At the confluence of the ducts, the caudal part of the primary outgrowth expands (ductus cystica), forming the gallbladder rudiment, which quickly lengthens, taking the form of a sac. From the narrow proximal part of this branch of the diverticulum, the duct of the bladder develops, into which many hepatic ducts open.

From the area of the primary diverticulum between the place where the hepatic ducts enter the duodenum, the common bile duct (ductus choledochus) develops. The distal, rapidly multiplying areas of the endoderm branch along the bile-mesenteric veins of early embryos, the spaces between the hepatic beams are filled with a labyrinth of wide and irregular capillaries - sinusoids, and the amount of connective tissue is small.

An extremely developed network of capillaries between the strands of liver cells (beams) determines the structure of the developing liver. The distal parts of the branching liver cells are transformed into secretory sections, and the axial strands of cells serve as the basis for the system of ducts through which fluid flows from this lobule in the direction of the gallbladder. A dual afferent blood supply to the liver develops, which is essential for understanding its physiological functions and clinical syndromes that arise when its blood supply is disrupted.

The process of intrauterine liver development is greatly influenced by the formation of the allantoic circulatory system, which is phylogenetically later than the yolk circulatory system, in the 4-6-week human embryo.

Allantoic or umbilical veins, penetrating the body of the embryo, are embraced by the growing liver. The passing umbilical veins and the vascular network of the liver fuse, and placental blood begins to flow through it. This is why during the intrauterine period the liver receives the blood richest in oxygen and nutrients.

After the regression of the yolk sac, the paired yolk-mesenteric veins are connected to each other by bridges, and some parts become empty, which leads to the formation of the portal (zygos) vein. The distal ducts begin to collect blood from the capillaries of the developing gastrointestinal tract and direct it through the portal vein to the liver.

A feature of blood circulation in the liver is that the blood, having once passed through the intestinal capillaries, is collected in the portal vein, passes a second time through the network of sinusoid capillaries and only then through the hepatic veins, located proximal to those parts of the yolk-mesenteric veins where the hepatic beams have grown into them, goes directly to the heart.

Thus, there is a close interdependence and dependence between the glandular liver tissue and the blood vessels. Along with the portal system, the arterial blood supply system, which originates from the trunk of the celiac artery, also develops.

In both adults and embryos (and fetuses), nutrients, after being absorbed from the intestines, first enter the liver.

The volume of blood in the portal and placental circulation is significantly greater than the volume of blood coming from the hepatic artery.

Liver mass depending on the period of development of the human fetus (according to V.G. Vlasova and K.A. Dret, 1970)

Age, weeks	Number of studies	Raw liver weight, g
5-6	11	0.058
7-8	16	0.156
9-11	15	0.37
12-14	17	1.52
15-16	15	5.10
17-18	15	11.90
19-20	8	18:30
21-23	10	23.90
24-25	10	30,40
26-28	10	39.60
29-31	16	48.80
31-32	16	72.10
40	4	262,00

The increase in liver mass is especially intense in the first half of human antenatal development. The fetal liver mass doubles or triples every 2-3 weeks. During 5-18 weeks of intrauterine development, the liver mass increases 205 times, during the second half of this period (18-40 weeks) it increases only 22 times.

During the embryonic period of development, the liver mass is on average about 596 of the body mass. In the early periods (5-15 weeks), the liver mass is 5.1%, in the middle of intrauterine development (17-25 weeks) - 4.9, and in the second half (25-33 weeks) - 4.7%.

By birth, the liver is one of the largest organs. It occupies 1/3-1/2 of the abdominal cavity volume, and its mass is 4.4% of the newborn's body mass. The left lobe of the liver is very massive by birth, which is explained by the peculiarities of its blood supply. By 18 months of postnatal development, the left lobe of the liver decreases. In newborns, the lobes of the liver are not clearly delineated. The fibrinous capsule is thin, there are delicate collagen and thin elastin fibers. In ontogenesis, the rate of increase in liver mass lags behind body mass. Thus, the liver mass doubles by 10-11 months (body mass triples), triples by 2-3 years, increases 5 times by 7-8 years, 10 times by 16-17 years, and 13 times by 20-30 years (body mass increases 20 times).

Liver weight (g) depending on age (no E. Boyd)

Age	Boys		Girls
	N	X	N	X
Newborns	122	134.3	93	136.5
0-3 months	93	142.7	83	133.3
3-6 months	101	184.7	102	178.2
6-9 mcc	106	237.8	87	238.1
9-12 months	69	293.1	88	267.2
1-2 years	186	342.5	164	322.1
2-3 years	114	458.8	105	428.9
3-4 years	78	530.6	68	490.7
4-5 years	62	566.6	32	559,0
5-6 years	36	591.8	36	59 U
6-7 years	22	660.7	29	603.5
7-8 years	29	691.3	20	682.5
8-9 years old	20	808,0	13	732.5
9-10 years	21	804.2	16	862.5
10-11 years	27	931.4	11	904.6
11-12 years old	17	901.8	8	840.4
12-13 years old	12	986.6	9	1048.1
13-14 years old	15	1103	15	997.7
14-15 years old	16	1L66	13	1209

The diaphragmatic surface of the liver of a newborn is convex, the left lobe of the liver is equal in size to the right or larger. The lower edge of the liver is convex, under its left lobe is the descending colon. The upper border of the liver along the right midclavicular line is at the level of the 5th rib, and along the left - at the level of the 6th rib. The left lobe of the liver crosses the costal arch along the left midclavicular line. In a child of 3-4 months, the intersection of the costal arch with the left lobe of the liver, due to a decrease in its size, is already on the parasternal line. In newborns, the lower edge of the liver along the right midclavicular line protrudes from under the costal arch by 2.5-4.0 cm, and along the anterior midline - 3.5-4.0 cm below the xiphoid process. Sometimes the lower edge of the liver reaches the wing of the right ilium. In children aged 3-7 years, the lower edge of the liver is located below the costal arch by 1.5-2.0 cm (along the midclavicular line). After 7 years, the lower edge of the liver does not emerge from under the costal arch. Only the stomach is located under the liver: from this time on, its skeletotopy is almost no different from the skeletotopy of an adult. In children, the liver is very mobile, and its position easily changes when the body position changes.

In children of the first 5-7 years of life, the lower edge of the liver always comes out from under the right hypochondrium and is easily palpated. Usually it protrudes 2-3 cm from under the edge of the costal arch along the midclavicular line in a child of the first 3 years of life. From the age of 7, the lower edge is not palpated, and along the midline should not go beyond the upper third of the distance from the navel to the xiphoid process.

The formation of liver lobules occurs in the embryonic period of development, but their final differentiation is completed by the end of the first month of life. In children at birth, about 1.5% of hepatocytes have 2 nuclei, while in adults - 8%.

The gallbladder in newborns is usually hidden by the liver, which makes it difficult to palpate and makes its radiographic image unclear. It has a cylindrical or pear-shaped form, less common is a spindle-shaped or S-shaped form. The latter is due to the unusual location of the hepatic artery. With age, the size of the gallbladder increases.

In children over 7 years of age, the projection of the gallbladder is located at the point of intersection of the outer edge of the right rectus abdominis muscle with the costal arch and laterally (in the supine position). Sometimes, to determine the position of the gallbladder, a line connecting the navel with the apex of the right axillary fossa is used. The point of intersection of this line with the costal arch corresponds to the position of the fundus of the gallbladder.

The midplane of the newborn's body forms an acute angle with the plane of the gallbladder, while in an adult they lie parallel. The length of the cystic duct in newborns varies greatly, and it is usually longer than the common bile duct. The cystic duct, merging with the common hepatic duct at the level of the neck of the gallbladder, forms the common bile duct. The length of the common bile duct is very variable even in newborns (5-18 mm). With age, it increases.

Average sizes of the gallbladder in children (Mazurin A.V., Zaprudnov A.M., 1981)

Age	Length, cm	Width at base, cm	Neck width, cm	Volume, ml
Newborn	3.40	1.08	0.68	-
1-5 mcc	4.00	1.02	0.85	3.20
6- 12 months	5.05	1.33	1.00	1
1-3 years	5.00	1.60	1.07	8.50
4-6 years	6.90	1.79	1.11	-
7-9 years	7.40	1.90	1.30	33.60
10-12 years	7.70	3.70	1.40
Adults	-	-	-	1-2 ml per 1 kg of body weight

The secretion of bile begins already in the intrauterine period of development. In the postnatal period, in connection with the transition to enteral nutrition, the amount of bile and its composition undergo significant changes.

During the first half of the year, the child mainly receives a fatty diet (about 50% of the energy value of breast milk is covered by fat), steatorrhea is quite often detected, which is explained, along with the limited lipase activity of the pancreas, to a large extent by the lack of bile salts formed by hepatocytes. The activity of bile formation is especially low in premature babies. It is about 10-30% of bile formation in children at the end of the first year of life. This deficiency is compensated to some extent by good emulsification of milk fat. The expansion of the range of food products after the introduction of complementary foods and then when switching to a regular diet places increasing demands on the function of bile formation.

Bile in newborns (up to 8 weeks) contains 75-80% water (in adults - 65-70%); more protein, fat and glycogen than in adults. Only with age does the content of dense substances increase. The secretion of hepatocytes is a golden liquid, isotonic with blood plasma (pH 7.3-8.0). It contains bile acids (mainly cholic, less chenodeoxycholic), bile pigments, cholesterol, inorganic salts, soaps, fatty acids, neutral fats, lecithin, urea, vitamins A, B C, and some enzymes in small quantities (amylase, phosphatase, protease, catalase, oxidase). The pH of gallbladder bile usually decreases to 6.5 against 7.3-8.0 of liver bile. The final formation of the bile composition is completed in the bile ducts, where a particularly large amount (up to 90%) of water is reabsorbed from the primary bile, and Mg, Cl, and HCO3 ions are also reabsorbed, but in relatively smaller quantities, which leads to an increase in the concentration of many organic components of bile.

The concentration of bile acids in the liver bile in children in the first year of life is high, then it decreases by the age of 10, and in adults it increases again. This change in the concentration of bile acids explains the development of subhepatic cholestasis (bile thickening syndrome) in children of the neonatal period.

In addition, neonates have an altered glycine/taurine ratio compared to school-age children and adults, in whom glycocholic acid predominates. Deoxycholic acid cannot always be detected in bile in young children.

The high content of taurocholic acid, which has a pronounced bactericidal property, explains the relatively rare development of bacterial inflammation of the biliary tract in children in the first year of life.

Although the liver is relatively large at birth, it is functionally immature. The secretion of bile acids, which play an important role in the digestion process, is small, which is probably often the cause of steatorrhea (a large amount of fatty acids, soap, and neutral fat are detected in the coprogram) due to insufficient activation of pancreatic lipase. With age, the formation of bile acids increases with an increase in the ratio of glycine to taurine due to the latter; at the same time, the liver of a child in the first months of life (especially up to 3 months) has a greater "glycogen capacity" than that of adults.

Content of bile acids in duodenal contents in children (Mazurin A.V., Zaprudnov A.M., 1981)

Age	Bile acid content, mg-eq/l		Glycine/taurine ratio		Ratio of acidic cholic/chenodeoxycholic/desoxycholic
	Average	Limits of oscillations	Average	Limits of fluctuations
Liver bile
1-4 days	10.7	4.6-26.7	0.47	0.21-0.86	2.5:1:-
5-7 days	11.3	2.0-29.2	0.95	0.34-2.30	2.5:1:-
7- 12 months	8.8	2.2-19.7	2.4	1.4-3.1	1.1:1:-
4-10 years	3.4	2.4-5.2	1.7	1.3-2.4	2.0-1:0.9
20 years	8.1	2.8-20.0	3.1	1.9-5.0	1.2:1:0.6
Gallbladder bile
20 years	121	31.5-222	3.0	1.0-6.6	1:1:0.5

The functional reserves of the liver also have pronounced age-related changes. In the prenatal period, the main enzyme systems are formed. They provide adequate metabolism of various substances. However, by birth, not all enzyme systems are mature enough. Only in the postnatal period do they mature, and there is a pronounced heterogeneity of the activity of enzyme systems. The timing of their maturation varies especially. At the same time, there is a clear dependence on the nature of feeding. The hereditarily programmed mechanism of maturation of enzyme systems ensures the optimal course of metabolic processes during natural feeding. Artificial feeding stimulates their earlier development, and at the same time, more pronounced disproportions of the latter arise.

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