Development of the Gastrointestinal Circulation in the Fetus and Newborn

Introduction

The intestine is a complex series of tissues, each with a specific role in digestion and excretion. For a mature intestine to function properly, it must protect its component cells from other organisms, including bacteria, viruses, and parasites, as well as from toxic substances. In addition, the intestine, in partnership with the liver and pancreas, disassembles potential nutrients and presents them (sugars, fats, proteins, vitamins, and minerals) to the liver for organization and distribution. Rapid cellular growth of the fetal intestine requires sufficient energy and a means for clearance of metabolic waste products. This is accomplished by a rapid and proportional growth of the intestinal circulation. As the solid intestine hollows and motility develops, amniotic fluid components—primarily the whey-like proteins—may be an additional source of substrate for growth of the proximal intestine.

Although anatomic and histologic studies have been performed on salvaged human fetal intestines, lack of availability of samples and autolysis has precluded detailed and systematic studies of the physiology of the developing gastrointestinal circulation. Therefore much of the information presented in this chapter is derived from controlled studies in animals. In addition, the most reliable data involve only that portion of the alimentary tract below the diaphragm, namely, the gastrointestinal and colonic circulation.

Several principles of gut development have an impact on intestinal blood flow. The cephalic portion of the embryonic intestinal tract develops and matures more rapidly than the caudal region. As the intestinal lining rapidly grows, the embryonic ileum is obliterated and eventually recanalizes. Although the intestine begins as a straight tube, differential growth rates result in the contrasting calibers of various gut segments and in the rotation and final positioning of various components.

The arterial supply to the intestine matures in response to its rapid growth. The majority of the intestinal tract mucosa, along with the liver parenchyma and pancreas, is derived from endoderm. In contrast, the connective tissue and muscular components are derived from splanchnopleuric mesoderm. Oral and anal epithelium is derived from the ectoderm of the stomatodeum and proctodeum, respectively. Progressing from the germ cell stage, the intestine is divided into three primary portions: the foregut, midgut, and hindgut. The foregut includes all structures distal to the tracheal diverticulum from the esophagus through the first half of the duodenum. The midgut is composed of structures distal to the second portion of the duodenum, including the jejunum, ileum, and proximal two thirds of the transverse colon. The hindgut consists of the distal transverse colon and the proximal two thirds of the anal canal.

Development of Intestinal Circulation

Early somite embryos have an extensive vascular network on the yolk sac. In the process of vasculogenesis, vascular endothelial precursor cells (angioblasts) migrate to the location of future vessels, coalesce into cords, differentiate into endothelial cells, and ultimately form patent vessels. When the primary vascular bed is formed, additional capillaries and vessels are added by angiogenesis, which is controlled by vascular endothelial growth factor (VEGF) and other stimulants such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF). Erythropoietin stimulates vasculogenesis in neonatal rat mesenteric microvascular endothelial cells. Unpaired ventral branches of the dorsal aorta (vitelline arteries) pass to the yolk sac, allantois, and chorion. The network drains by way of the vitelline veins to the heart. During the fourth week, the primitive gut is formed as the dorsal portion of the yolk sac is incorporated into the embryo. Three vitelline arteries persist to supply the foregut (celiac artery), midgut (superior mesenteric artery), and hindgut (inferior mesenteric artery).

The vessels distributed to the foregut fuse and form a single vessel, the celiac artery. With a downward migration of the viscera, the aortic attachment of the celiac artery moves caudally. It divides into the hepatic artery, splenic artery, and left gastric branches to supply the stomach and duodenum. The liver, pancreas, and related mesodermal spleen receive their blood supply from these branches. At the vascular division between the foregut and midgut is the anastomosis between the superior pancreaticoduodenal and the inferior pancreaticoduodenal arteries.

The embryonic vitelline arteries fuse and form a superior mesenteric trunk, which reaches the midgut by passing through the mesentery. Terminal branches of this trunk supply the yolk sac. The various branches distal to the intestine are obliterated when the ileum separates from the yolk sac and vitelline stalk. However, the superior mesenteric artery remains and supplies the intestinal circulation from the second part of the duodenum through the proximal two thirds of the transverse colon. ^,

The ventral branches of the aorta supplying the hindgut fuse to form a single inferior mesenteric trunk. Its final distribution includes the distal one third of the transverse colon and the entire descending colon and sigmoid. The inferior mesenteric trunk anastomoses with the middle colic artery, which is a branch of the superior mesenteric artery. Distal to this is an anastomosis to branches of the inferior and middle rectal arteries from the internal iliac trunk. ^,

Venous Drainage of the Gastrointestinal Tract

The venous drainage of the intestine is much more variable than is the arterial blood supply. The low-pressure venous drainage in the embryo is plexiform, and therefore patency is based somewhat on blood flow. In addition, blood has a tendency to seek the most direct route of flow due to hydrodynamic factors.

The vitelline veins initially pass along each side of the anterior intestinal portal vein. They form an anastomotic plexus around the developing duodenal loop in the tissue of the septum transversum. Cords of liver cells extend into the septum transversum and divide the vitelline plexus into the primitive hepatic sinusoids. Anterior stems of the vitelline veins enter the primitive sinus venosus. As the stomach, duodenum, and small intestine elongate and rotate from their original midsagittal position to the adult position, blood flow develops along the most direct route to the liver, cutting from one vitelline vein to another through the connecting plexus. Consequently, the portal venous system does not develop in a spiral fashion around the developing intestine but instead evolves short and straight with the duodenum and intestine around it. ^,

In embryos of less than 5-mm crown-rump length (<5 weeks), blood from the paired umbilical veins passes into the liver, at which point it communicates with the vitelline sinusoids. At a 7-mm crown-rump length (33 to 34 days), the right umbilical vein atrophies and disappears. As a result, all the placental blood entering the embryo enters through the left umbilical vein and empties into the hepatic sinusoids. As the right side of the sinus venosus elaborates, an enlargement of the hepatic sinusoidal communication occurs between the right hepatocardiac channel and the left umbilical vein forming the ductus venosus. Thus blood entering from either the umbilical or vitelline systems can pass by way of the ductus venosus to the right atrium or into the liver sinusoids. The venae advehentes, connecting the umbilical and vitelline systems to the hepatic sinusoids, become the branches of the portal vein in the liver. In addition, the venae revehentes connecting the sinusoids to the right hepatocardiac channel become the tributaries to the hepatic veins. After birth the left umbilical vein and the ductus venosus are obliterated and become the ligamentum teres and the ligamentum venosum, respectively.

The Intestinal Microcirculation

The microscopic anatomy of the intestinal circulation varies from species to species. In rabbits and humans, villus arterioles ascend from the submucosal arterioles into the villus. Distribution of blood flow within the intestinal wall is not uniform but appears to follow a pattern of functional importance of the tissue layer ( Fig. 48.1 ). At a resting stage without feeding, the mucosal layer (the primary site of absorption) receives approximately 70% of the intestinal blood flow, while the muscular and serosal layer receives approximately 25% and the submucosa receives 5%. As the arteriole reaches the villus tip, it divides into a diffuse capillary network, which then drains into a centrally located villus venule originating in the distal one third of the villus. In most mammals, the capillaries of the intestinal villus are fenestrated. Just as the villus and the microvillus are exposed to a large solute and water load, so the villus capillaries must be capable of handling the absorbed nutrients. The endothelium of the capillary facing the epithelium is very thin and usually contains fenestrae, with the greatest number at the villus tips and in the crypts.

Water and solutes are transported into the capillary by a number of different pathways ( Fig. 48.2 ). Low-molecular-weight nonpolar substances and lipid-soluble substances such as oxygen and carbon dioxide may cross directly through the cell membrane. The bulk of absorbed materials passes through fenestrae, which are numerous circular openings of up to 30 nm in the capillary endothelium and may be either opened or diaphragmed. At least 60% of the fenestrae have a diaphragm. Although the porosity is not known, these diaphragms limit the movement of molecules. Much less commonly, water and solutes move slowly by pinocytosis. In this process, vesicles are formed that move through the cell to the opposing side before releasing their contents. On rare occasions, transendothelial channels may be formed when several vesicles simultaneously open and bridge the cell. These occurrences are relatively infrequent and do not have a major impact on total absorptive capacity. Intercellular junctions are impermeable to solutes of 2-nm diameter in the arteriole and capillary but may play a limited role in venule absorption.