Formation of the liver and biliary tract during embryogenesis

A liver with a duct system and a gallbladder develop from the hepatic diverticula of the ventral endoderm of the primary midgut. The onset of liver development is the 4th week of the intrauterine period. Future proximal bile ducts form from the proximal diverticulum, and the hepatic beams from the distal duct.

Rapidly multiplying endodermal cells of the cranial part (pars hepatica) are introduced into the mesenchyme of the abdominal mesentery. Mesothermal sheets of the abdominal mesentery with the growth of the liver diverticulum 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. At the 6th week, luminal gleams of the hepatic beams, the "bile capillaries," become visible. At the site of the fusion of the ducts, the caudal part of the primary outgrowth expands (ductus cystica), forming a bookmark of the gallbladder, which rapidly lengthens, taking the shape of a sac. From the narrow proximal part of this branch of the diverticulum, the duct of the bladder develops, where a number of hepatic ducts open.

A common bile duct (ductus choledochus) develops from the site of the primary diverticulum between the place of confluence of the hepatic ducts and the duodenum. Distal rapidly multiplying sites of the endoderm branch along the course of the biliary mesenteric veins of early embryos, the spaces between the hepatic beams are filled with a maze of wide and irregular capillaries - sinusoids, but the amount of connective tissue is small.

An extremely developed network of capillaries between the strings of the hepatic cells (beams) and determines the structure of the forming liver. The distal parts of the branching liver cells are transformed into secretory sections, and the axial cords of the cells serve as the basis of the duct system, through which fluid flows out from this lobe to the gallbladder. A double afferent blood supply of the liver is developing, which is essential for understanding its physiological functions and the clinical syndromes that arise when its blood supply is disturbed.

The process of intrauterine development of the liver is greatly influenced by the formation in a 4-6-week-old embryo of a person phylogenetically later than the yolk, allantoic circulation.

Allantoic, or umbilical, veins, penetrating the body of the embryo, are covered by a growing liver. There is a fusion of passing umbilical veins and a vascular network of the liver, and placental blood begins to pass through it. That is why in the prenatal period the liver receives the most rich in oxygen and nutrients blood.

After regression of the yolk sac, the paired yolk-mesenteric veins are connected to each other by bridges, with some parts emptying, which leads to the formation of a portal (unpaired) vein. 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 peculiarity of the blood circulation in the liver is that the blood that has already passed through the intestinal capillaries gathers into the portal vein, passes through the network of capillaries-sinusoids again and only then through the hepatic veins located proximal to those parts of the yolk-mesenteric veins where hepatic beams, goes directly to the heart.

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

As in an adult, and in an embryo (and fetus), nutrients after absorption from the intestine first enter the liver.

The blood volume of the gates and placental circulation is much larger than the volume of blood coming from the hepatic artery.

Weight of the liver depending on the period of development of the human fetus (according to VG Vlasova and KA Dret, 1970)

Age, week	Number of studies	Mass of crude liver, g
5-6	Eleven	0.058
7-8	16	0.156
9-11	15	0.37
12-14	17th	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 antenatal development of a person. The weight of the fetal liver doubles or triples every 2-3 weeks. Within 5-18 weeks of intrauterine development, the liver mass increases by 205 times, during the second half of this period (18-40 weeks) it increases only 22 times.

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

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

Liver weight (g) as a function of 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 mss	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 old	36	591.8	36	59 U
6-7 years	22	660.7	29	603.5
7-8 years old	29	691.3	20	682.5
8-9 years	20	808.0	13	732.5
9-10 years old	21	804.2	16	862.5
10-11 years old	27th	931.4	Eleven	904.6
11-12 years old	17th	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 the newborn is convex, the left lobe of the liver is equal in size to the right one or exceeds it. The lower edge of the liver is convex, under its left lobe is the descending colon. The upper border of the liver on the right sredneklyuchichnoy line is at the level of V rib, and on the left - at the level of the VI rib. The left share of the liver crosses the costal arch along the left middle clavicle line. At the child 3-4 months the place of crossing of the costal arch with the left lobe of the liver due to the decrease in size is already on the pericarp line. In newborns, the lower edge of the liver on the right sredneklyuchichnoy line protrudes from beneath the costal arch by 2.5-4.0 cm, and along the anterior median line - by 3.5-4.0 cm below the xiphoid process. Sometimes the lower edge of the liver reaches the right ilium bone. In children 3-7 years, the lower edge of the liver is below the costal arch by 1.5-2.0 cm (on the mid-incision line). After 7 years, the lower edge of the liver from under the costal arch does not come out. Under the liver is only the stomach: since this time, its skeletal tootopy almost does not differ from the skeletonotopia of an adult. In children, the liver is very mobile, and its position easily changes when the position of the body changes.

In children of the first 5-7 years of life, the lower edge of the liver always leaves from under the right hypochondrium and is easily probed. Usually it protrudes 2-3 cm from under the edge of the costal arch along the mid-succinic line in the child of the first 3 years of life. From the age of 7, the lower edge is not palpable, and on the median line should not extend beyond, the upper third of the distance from the navel to the xiphoid from the sprout.

Formation of lobules of the liver occurs in the embryonic period, 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 it is 8%.

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

In children after 7 years, the projection of the gallbladder is at the point of intersection of the outer edge of the right rectus muscle with the costal arch and lateral (in the supine position). Sometimes, to determine the position of the gallbladder, a line connecting the navel to the apex of the right axilla is used. The point of intersection of this line with the costal duvet corresponds to the position of the bottom of the gallbladder.

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

The average size of the gall bladder in children (Mazurin AV, Zaprudnov AM, 1981)

Age	Length, cm	Width at base, cm	Width of neck, cm	Volume, ml
Newborn	3.40	1.08	0.68	-
1-5 mss	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 old	6.90	1.79	1.11	-
7-9 years	7.40	1.90	1.30	33.60
10-12 years old	7.70	3.70	1.40
Adults	-	-	-	1 -2 ml per 1 kg of body weight

Bile secretion 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 mostly receives a fat diet (about 50% of the energy value of women's milk is covered by fat), steatorea is often detected, which, in addition to the limited lipase activity of the pancreas, is largely due to a lack of bile acid salts formed by hepatocytes. Especially low the activity of bile formation in premature babies. It is about 10-30% of the bile in children at the end of the first year of life. This deficit is compensated to some extent by a good emulsification of milk fat. Expansion of the food package after the introduction of complementary foods and then, when switching to a normal diet, there are increasing demands on the function of bile formation.

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

The concentration of bile acids in hepatic bile in children of the first year of life is high, then it decreases to 10 years, 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, in newborns, the glycine / taurine ratio has been altered compared to school-age children and adults with predominantly glycocholic acid. Children of early age in bile do not always find deoxycholic acid

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 of the first year of life.

Though to a birth the liver is rather great, it in the functional attitude is immature. Isolation of bile acids, which play an important role in the process of digestion, is small, which probably serves as the cause of steatorrhea (a coprogram reveals a large number of fatty acids, soap, neutral fat) due to inadequate activation of the pancreatic lipase. With age, the formation of bile acids increases with an increase from glycine to taurine at the expense of the latter; at the same time, the baby's liver of the first months of life (especially up to 3 months) has a greater "glycogen capacity" than adults.

The content of bile acids in duodenal contents in children (Mazurin AB, Zaprudnov AM, 1981)

Age	The content of bile acids, mg-eq / l		The glycine / taurine ratio		With otnoshenne acid cholecha / chenodezoxycholic / dezokenholovaya
	Average	vibration limits	Average	fluctuation limits
Hepatic 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
Bubble bile
20 years	121	31.5-222	3.0	1.0-6.6	1: 1: 0.5

Functional liver reserves also have pronounced age-related changes. In the prenatal period, the basic enzyme systems are formed. Providing an adequate metabolism of various substances. However, not all enzyme systems are mature enough to be born. Only in the postnatal period is their maturation, and marked heterogeneity of the activity of enzyme systems. Especially the timing of their maturation. 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 with natural feeding. Artificial feeding stimulates their earlier development, at the same time there are more pronounced disproportions of the latter.

[1], [2], [3], [4], [5], [6], [7]