LORI.equine

Fetal-placental circulation and the question of lymphatic drainage

Keywords: blood supply, vessels, equine, placenta, umbilical, artery, vein, urachus

Figure 1 shows how the umbilical arteries on either side of the bladder course towards the umbilical cord. These arteries of course, differ from those in the postnatal animal because they carry de-oxygenated blood. Because umbilical arteries transport blood under high pressure, they have a histological structure i.e. thick walled and elastic, similar to arteries in postnatal animals.  Figure 1 also shows how the bladder lies between the umbilical arteries and merges cranially into the urachus.

Figure 1. Arterial circulation and urine flow entering the umbilical cord. Image size: 1442 x 692 px

A brief review of fetal circulation: During gestation, oxygenated blood from the placenta enters the liver via the umbilical vein but there are species variations in that regard. In horses (and pigs) it does not course through the liver as a single major vessels (as is the case in most animals). Instead, the umbilical vein splits into several veins that perfuse the liver which then pass into the posterior vena cava. In other animals the liver is only partially perfused by the umbilical vein and then, only on one side, not the other. This for example, is true of sheep where only the left lobe of the liver is supplied by the umbilical vein, while the right lobe is supplied by portal venous branches. With no need for oxygenation by the fetal lungs, two thirds of this blood bypasses the right ventricle through the foramen ovale, entering the left ventricle and returning to the peripheral circulation. Any blood that leaves the right heart via the pulmonary artery, is shunted into the aorta via the ductus arteriosis. The foramen ovale begins to close at about 320 days of gestation and should close completely by 4 days postpartum. After birth, the umbilical vein and both umbilical arteries collapse. The umbilical arteries form the round ligaments on either side of the bladder and the umbilical vein forms the round ligament within the falciform ligament of the liver. The latter is so called because of its resemblance to a scythe (> Latin falx meaning sickle or scythe). For this, we thank the fruitful imagination of some long lost anatomist. For an excellent diagram of fetal circulation, see Wilsher, S. et al. 2011.

The arborized venules and veins of the placenta converge into a few major veins then finally, into a single umbilical vein within the amnionic portion of the umbilical cord. Therefore, the umbilical cord proximal to the fetus (within the amnion) contains only three major blood vessels; two arteries and one vein. Several abnormal variations on this theme have been described in humans by various authors and in the horse by Wilsher, S. et al. 2011. In normal specimens, these vessels are shown in figure 3 and another LORI entry as well.

Figure 2 shows the umbilical vein coursing into the liver. In the fetus it delivers oxygenated blood to the fetus.

Figure 2. Fetal circulation from the placenta showing the umbilical vein entering the liver from the umbilical cord. Image size: 1367 x 647 px

The histology of vessels in the umbilical cord is interesting. As mentioned earlier, the presence or absence of oxygenated blood has little effect on their structure when compared to arteries and veins within the body of the fetus. Blood pressure appears to be the dominant factor in their structure. In figure 3, one can appreciate that situation. 

Figure 3: A cross section of an umbilical cord from within the amnion, taken approximately 12 hours after foaling. The parity of the mare is not known. Image size: 1727 x 1336 px 

In figure 3, note the two thick-walled umbilical arteries (one torn during foaling) and the much larger, thin-walled umbilical vein. Also note the voluminous urachus. The urachus is virtually absent in humans because the allantois is reduced to a vestigial structure within the umbilical cord. Finally, note the relative absence of Wharton's jelly in comparison to humans as well.  

About Wharton's jelly: Wharton's jelly is a mucopolysaccharide substance akin to the vitreous humor in the eye. Perhaps some are aware that Wharton's jelly was named for Thomas Wharton, an English Physician of the mid 17th century. Certainly, this author was not. Even more surprising, was that another structure far from the reproductive tract also bears his eponym; the duct of the sub-mandibular salivary gland! The tunica adventitia in all animals provides strengthening around umbilical blood vessels throughout the body. Strangely, in humans, it is only umbilical vessels that lack the tunica adventitia. In this entry, the tunica adventitia is obvious around the equine umbilical vein and arteries In humans by contrast, Wharton's jelly is thought to provide support to the blood vessels in the absence of the tunica adventitia. Despite a comprehensive search, the author was not able to retrieve publications on Wharton's jelly in primates but presumes its presence and nature is similar to that in humans. Wharton's jelly serves as a significant research and commercial source for fetal stem cells in humans. This may occur in veterinary medicine as well. In fact, stem cells were recently harvested from the umbilical cord of a newborn foal and used to enhance wound healing in an adult horse. Despite the interest in harvesting stem cells from the umbilical cord, little is known about where one should harvest multi-potential cells within a cross section of the cord in either humans or animals. Data reviewed by Davies. J.E. et al. show that the area around the umbilical blood vessels may be richest in these valuable cells. Although significant structural differences exist between species and Wharton's jelly is not obvious in domestic animals, it seems logical to suggest that perivascular areas be harvested for use in horses.

Tissue was examined at high magnification from three sites as shown in figure 3.They are labelled A, B and C. See below.

Figure 3 A: Area A; a high power section of the wall of the umbilical vein.  Note the predominance of collagenous tissue, the presence of an interposing smooth muscle layer and the absence of elastic tissue. Image size: 1904 x 1168 px

Figure 3B: Area B; a high power section of the wall of the umbilical artery. Note the predominance of smooth muscle layers and elastic tissue. Collagenous tissue is present as well but does not predominate as it seen in the umbilical vein. Image size: 1904 x 1258 px

Figure 3C: Area C. Note that the urachus is lined by both simple cuboidal and transitional epithelium. One will recall that the rest of the urinary tract is mostly lined with transitional epithelium. Despite being part of the urinary tract in the fetus, the allantois is lined with simple cuboidal epithelium. Image size: 2000 x 1150 px

The image below shows the infused blood supply to the chorioallantois (allantochorion). Because of space restriction in the infusion vessel, the placenta was not laid out in the traditional "F" shape for examination. Part of the amnion was torn away before the author retrieved the specimen. An intact amnion is shown in figure 8.

Figure 4. The blood supply and drainage in a placenta from a normal foaling. The venous system has been injected with red dye and emphasized digitally for clarity. The arteries remain off-white in color. The placenta is viewed from its allantoic surface. Image size: 2459 x 1424 px

In figure 4, the umbilical vein was infused with dye for facility. This is a large vessel and easy to catheterize for infusion.  No thought was given to the fact that veins usually have valves and as such, would have prevented back-flow of the dye into the vascular network. Unexpectedly, the veins filled with dye easily, with no evidence of valvular occlusion. This suggested the absence of valves in the placental veins. Upon researching this possibility, the author was surprised to learn that placental veins in other species are indeed devoid of valves; an interesting physiological situation on which to speculate. The author dissected some major veins and tributaries. Indeed, as shown in figure 5, no valves were seen in those vessels.

Figure 5: Three sections of placental veins from the allantochorion sampled at random, showing the absence of valves. Image size: 1914 x 1156 px

Figure 6a: A network of arterioles and venules beneath the allantoic membrane viewed from within the allantois. Capillaries (5 to 10 microns in diameter) are not visible at this magnification. Image size: 1967 x 1227 px

Figure 6b: This image shows the macroscopic similarity between veins and arteries in the allantochorion. The exclamation mark next to the vein label shows that this was unexpected. Image size: 2000 x 1234 px

Placental veins carry oxygenated blood therefor one might expected them to be more red in appearance than the veins. Following the umbilical vein to its tributaries in figure 6b, this was not the case. 

In figure 6a, note how the majority of small vessels run parallel to one another. This is reminiscent of capillary architecture in villi of the microcotyledons; elegantly illustrated by Abd-Elnaeim et al. 2006 using corrosion casting and scanning EM. Parallel placement of vessels against a transfusion surface (the chorion in this case) provides for efficient transfusion of gasses, waste and nutrients. All these vessels are closely adherent to the chorion. The allantoic membrane by contrast, is loosely attached to the chorion and can easily be detached from the chorion. This can be seen around the larger vessels in figure 6, where water from the infused vessels has split the allantois from the chorion. This observation is substantiated in figure 7 sampled from a non-infused placenta.

Figure 7: A cross section of the allantochorion showing the location of major blood vessels adjacent to the chorion, not the allantois. In terms of placental function, this would be expected. In this case, placental vessels were not infused in any manner, yet the tenuous connection between allantois and chorion is obvious. This may be an important factor with regard to the formation of allantoic cysts as discussed elsewhere in LORI (pending). Image size: 1436 x 1320 px

Figure 8: A cross section of the allantoic membrane, showing the small vessels that serve that structure. There appear to be few major vessels serving the allantois. It is likely that this is the case because the allantois is a storage structure for waste products, requiring little or no transfusion system. In all probability, small vessels are required for the structural integrity of the allantoic membrane alone. Image size: 1085 x 1315 px

Figure 8: This placenta shows the expected distribution of arteries and veins in the amnioallantois (usually abbreviated to amnion). The yellow arrow indicates where urine flow would have emerged from the urachus. The large, rejected endometrial cups (allantoic polyps) are discussed elsewhere in LORI (pending). Image size: 1085 x 1315 px

As expected, the vascularity in the amnion is sparse compared to that in the allantochorion. This is perhaps even more obvious in figure 4 than figure 8. The vascular supply to the amnion serves only the integrity of two fused, and relatively simple membranes. The supply to the allantochorion serves the complex nutritional, excretory, secretory and respiratory interface between the dam and fetus. 

Lymphatic drainage from the placenta

In essence, the placentas in horses, humans and other animals lack lymphatic systems. The placenta contains neither lymphatic vessels nor lymph nodes. What then is the mechanism for draining interstitial fluid from the placenta?  

Tissues throughout the body are of course, sustained by the presence of interstitial fluid provided by capillaries. Of the total amount of interstitial fluid delivered by capillaries, approximately 85% enters the venules under the effect of osmotic pressure. The remaining fluid drains into blind-ended lymphatic vessels and immediately becomes known as lymph, although its composition is essentially the same as interstitial fluid.

It is not known how the placenta deals with drainage of interstitial fluid. However it may be safe to assume that the absorptive character of the placenta itself (transfusing fluid from the maternal circulation) partially represents the function of the lymphatic system in the placenta. The remaining fluid in interstitial spaces may be absorbed directly into the vasa vasori of placental veins. This subject in addressed in another LORI entry (pending).

For this entry, the author wishes to acknowledge the assistance of colleagues Drs T. Muirhead and G.Wright, Dr Martha Mellish for collecting specimens and the global technical support from the AVC post mortem laboratory and quality assurance programs.

Selected references:

Abd-Elnaeim et al. 2006 Structural and hemovascular aspects of placental growth throughout gestation in young and aged mares. Placenta 27:1103-1113

Arpi, L.M.B. 2018. Histology of Umbilical Cord in Mammals http://dx.doi.org/10.5772/intechopen.80766

Bellini, C. et al. 2012. Are there lymphatics in the placenta? Lymphology 45:34-36

Castro, E. et al. 2011. Neither normal nor diseased placentas contain lymphatic vessels. Placenta 32:310-316

Davies. J.E. et al. 2017. Concise review: Wharton’s Jelly: The rich, but enigmatic, source of mesenchymal stromal cells. Stem cells translational medicine. 6:1620–1630

Ebrahim EI-Nefiawy, N. 2017. Development of Human Umbilical Vessels in The Second Trimester of regnancy: Histological, Immunohistochemical and Morphometric study. DOI:10.21608/EJH.2017.4079

Edelstone, D.I. et al. 1978 Liver and ductus venosus blood flows in fetal lambs in utero. Circulation research 42: 426-443

Faber, J.J. and Anderson, D.F. 2002. Am J Physiol Heart Circ Physiol 282:H850–H854

Girodroux, M. et al. 2019. A single umbilical artery and omphalophlebitis in an Arabian foal. Equine Vet. Educ. 31:6-12

Lanci, A. et al. 2019. Heterologous Wharton's Jelly Derived Mesenchymal Stem Cells Application on a Large Chronic Skin Wound in a 6-Month-Old Filly. Front. Vet. Sci., 30 January 2019 | https://doi.org/10.3389/fvets.2019.00009

Spivack, M. 1946. The anatomic peculiarities of the human umbilical cord and their clinical significance Am.J.Ob.Gyn. 52:387-401

Stehbens, W.E. et al. 2005. Histopathology and ultrastructure of human umbilical blood vessels.
Fetal Pediatriatric Pathol. 24:297-315.

Slater, S. 2005. Patent ductus arteriosus in a 9-day-old Grant’s zebra. Can Vet J. 46:647–648

Wilsher, S. et al. 2011. Three types of anomalous vasculature in the equine umbilical cord.Equine Vet. Educ. 23:109-118