Paper - Arrest of Development of an Embryo. A Case of Acephalus Holoacardiacus showing Arrest of Development of all Tissues in Embryonic Period

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Boulgakow B. Arrest of Development of an Embryo. A Case of Acephalus Holoacardiacus showing Arrest of Development of all Tissues in Embryonic Period.. (1926) J Anat. 61(1): 68-93. PMID 17104128

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This historic 192 paper by Boulgakow describes the abnormal development of a human embryo lacking a head.




Modern Notes: head abnormalities

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Arrest of Development of an Embryo. A Case of Acephalus Holoacardiacus showing Arrest of Development of all Tissues in Embryonic Period

By Boris Boulgakow, M.D.

Curator of Museums, Royal School of Medicine, Cairo

Introduction

The specimen was brought from the Department of Public Health on 3rd November, 1922. This monster was born together with a female twin at full term and normally developed. The parents are Egyptians, who are in good health and strong. They state that there has never been any similar case in the family. The father is a carpenter. The mother 30 years old and married since the year 1910. Her menses are usually normal. She passed through seven pregnancies; the first five children were normally developed, but they all died aged between 1 and 8 years; the sixth child, a girl, is living and is now 8 years old; the seventh pregnancy was the last and continued 9 months. During this last pregnancy, the mother felt the quickening as usual and she said that she never remarked any difference in comparison with other pregnancies except that she was “‘ weaker” in this last one. The normal twin was born first and then the monster. The weight of the monster is about 700 gm.; all the body is covered with smooth skin. There is no head, but the head end is enlarged and rounded; on the anterior surface there is a depression bounded laterally by two folds between which there is a small gelatinous structure, representing the head. Above the depression there are a few hairs.


Fig. 1. Fig. 2. Acephalus holoacardiacus, anterior aspect. Acephalus holoacardiacus, posterior aspect.


In the abdominal region there is an open umbilical ring, containing the umbilical cord and coils of intestines; and in the pubic region there is a structure resembling somewhat a penis. The lower extremities are well developed. The length of the monster from the upper pole to the heel is 254 cm. Its widest diameter is 11 cm.; the inter-cristal diameter is 8} cm. The length of left lower extremity is 12 cm. and the right 11 cm.

In consideration of the fact that the study of such a monstrosity as an acephalic holoacardiac foetus gives us a good idea as to the development of the embryo as a whole and may help us to understand and explain some difficult questions of development of different tissues, I am going to describe particularly some tissues, because they show early stages of development; the circulation, because of its going in an opposite direction to that in the normal foetus; the thoracic cavity which is empty; the abdominal and pelvic cavities for their evidences of arrest of development; and the central nervous system which shows degeneration.

The Skin

There is an external covering of skin and a markedly oedematous subcutaneous stratum; below this is a dense layer of adipose tissue, divided up into lobules by bands of connective tissue; under that is a layer of dense tissue resembling deep fascia. There was no evidence of hair with the exception of a few which may be seen on the upper part of the monster which represents the head. Microscopically a section from the abdominal wall is seen to contain a thin layer of epithelial cells composed of only two or three layers of cells; in this epithelium we can recognise the stratum corneum and stratum mucosum. Under this was a layer of connective tissue with a markedly oedematous Malpighian layer and subcutaneous tissue. In the second section taken from the lower limb all appearances are better shown; here may be seen the stratum corneum, lucidum, mucosum, the subcutaneous tissue, the mouths of hair follicles with the papillae and sebaceous glands in a state not fully complete; then a dense layer of adipose tissue. All structures are very oedematous and no sweat glands can be seen.

The Musculature

The muscular system has not attained full development and is degenerated. Its appearance is not like that of normal muscle; it is difficult to recognise it from other tissues. The muscles cannot be separated because they are fused with other tissues, especially in the trunk. The muscles of the lower extremities have the same appearance, but as the tendons are well developed ' one can follow the direction of groups of muscles which latter cannot be separated one from the other. If a transverse section is made through such a muscle, there is seen an outer layer of muscular fibres investing layers of fatty tissue; this may be the result of fatty degeneration in the inner layers. Under the low power, fibres of muscles taken from the calf of the leg or the back of the trunk are seen widely separated, with fatty tissue filling the interspaces. Separate muscular fibres are not completely differentiated and no striation can be seen; they look more like smooth muscle fibres. Tendons and ligaments are developed in the trunk as well as in the lower extremities.

The unstriped muscle fibres in the body are developed comparatively to a high degree and thus may be recognised easily in the small intestine.

It is known that the cross-striated and smooth musculature with a few exceptions arise from the mesoderm. The cross-striated and smooth fibres are not to be considered as fundamentally different, they merely represent different grades of development, likewise different paths of differentiation from a common fundamental form.

Mareshini and Ferrari found that in the early stages of development smooth and cross-striated filaments show exactly the same structure. It has been commonly supposed that the first differentiation of the muscles from the mesoderm takes place under the influence of the nervous system through the agency of the motor nerves, and that self-differentiation of muscles does not occur. It is known that the motor nerves unite very early with the developing myotomes and muscular masses. According to Neuman’s studies of acephalic and amyelic monsters, the influence of the motor nerves is necessary for the differentiation of the muscular system. Leonova has described a human monster without brain and spinal cord in which the peripheral sensory nerves and musculature were normally developed; but Weber and Neuman have described cases in which absence of certain portions of the central nervous system has been accompanied by the total absence of musculature which is normally supplied by the lacking nerves, although skeleton, blood vessels and even tendons were normally developed. Neuman would explain these apparent differences by assuming that muscles first arise under the influence of the central nervous system, but that their nourishment and further growth during the embryonic period takes place independently of the central nervous system and not until post-embryonic life is reached is the dependence again established. Thus the nervous system must have developed in the early stages of embryonic life up to a certain point and undergone degeneration after differentiation of the muscular system had taken place.

Keibel points out that in the embryos of lower vertebrates, the connection of the motor spinal nerves with the muscle plates is established just at the time when the contractile substance begins to be laid down, but in the pig, according to Barden, the musculature is differentiated to a considerable extent before the nerves establish a connection with it.

Harrison removed the spinal cord in a series of frog embryos before the histological differentiation in either the muscular or nervous system had begun, so that isolation of the musculature from the nervous system was complete. Still the differentiation of contractile substance took place in the normal manner, as did the grouping of the fibres into individual muscles.

At how early a period in the development of the ovum this power of self-differentiation of muscular tissue begins, is problematical. In consideration of the fact that the muscular tissue in our case is slight in amount and that it has not passed through the period of differentiation, we suggest that the musculature is in an embryonic state as a result of arrest of development of the embryo. Both motor and sensory nerves are well developed and can be seen going to the muscles and periphery, supplying all tissues.

In spite of the presence of nerves to the tissues and vessels, there is no evidence of normal development, only an increase in size of muscular tissue. This suggests the idea that some organ, which should regulate the growth of muscular tissue and complete its development, is absent.

Accordingly we may agree with the suggestion of Neuman and Harrison that growth and nourishment proceed independently until the post-embryonic period begins, when dependence on the central nervous system should be established. If this does not take place, we should expect an arrest of development of muscular tissue, as is the case in the acephalus holoacardiacus we are describing.

The Circulation

The circulation of blood in acardiacus has been the subject of much discussion, particularly owing to the absence of the heart, which makes it difficult to understand how that phenomenon goes on.

Generally acardiacus is one of twins, and as it always has an umbilical cord, we may say that the deformed twin is dependent upon the placental circulation.

Before discussing the different theories of circulation in the acardiacus we will describe the complete distribution of vessels in our case.

The umbilical cord. The umbilical cord is 9 cm. in length and 4 mm. thick; it enters through the umbilical ring with coils of intestines. It looks like a 72 Boris Boulgakow

normal cord but thinner and shorter. The microscopic appearances are exhibited in fig. 8. The cross-section was taken from the middle of the cord; there is the sheath, consisting of stratified epithelium; the outer layer of cells is corneous. Within the sheath the vessels of the cord are held together by an embryonic connective tissue, Wharton’s jelly. There are four vessels— two arteries and two veins. The umbilical vessels are composed almost entirely of a middle muscular coat, being simply muscular tubes; the tunica intima is rudimentary, there is no tunica adventitia, and no elastic tissue, but muscular fibres run in various directions. The outer surface of the muscular coat is seen passing into the surrounding Wharton’s jelly.


Fig. 3. Cross-section through the umbilical cord of acardiacus.

On dissection we can follow the direct path of these four vessels. The vessels were injected—one artery and one vein—in the abdominal cavity just after leaving the umbilical ring.

The X-ray photo (fig. 4) shows that the vascular system is well developed and distributed equally; there is no evidence of vessels for the liver, spleen or stomach. In the thoracic cavity only the dorsal aorta is present without any traces of the heart. We used this X-ray photo as a guide during dissection.

Fig. 5, which is schematic, shows as far as possible the distribution of vessels in different regions.

From the umbilical cord (fig. 5) two vessels pass towards the body, these are the umbilical arteries. These two vessels are seen passing on both sides of the urachus and allantois giving branches to the latter, then they give branches to the lower extremities—arteriae ischiadicae, femoralis, saphena magna—and small branches to the neighbouring structures. Arteria ischiadica is a huge vessel which arises from the lower part of the umbilical artery and runs with the sciatic nerve, which partly surrounds it. After giving branches | for the thigh and knee joint it divides into anterior and posterior tibial arteries in the same manner as the popliteal artery. The femoral artery is a short vessel which goes with the femoral nerve and gives a branch, accompanying the saphenous nerve—art. saphena magna.


The umbilical arteries turn sharply backwards and when the left umbilical artery receives the right one, which latter passes behind the cloaca, the two continue as one main trunk—the dorsal aorta. In its course the aorta gives branches to the large and small intestines, to the kidneys and suprarenal glands; and in its ascent it is more to the left side of the body, where it gives intercostal arteries and ends at the level of the 5th thoracic vertebra in two big branches which diverge and pass on each side of the vertebral column. The branch of the right side passes under the clavicle of that side and then gives three small branches towards the cervical vertebrae and towards the head end of the body; then the main artery ends on the dorsal aspect of the first thoracic vertebra just under the skin; the branch of the left side takes the same course and gives the same branches and, when it ends dorsal to the first thoracic vertebra, anastomoses with its fellow of the right side (fig. 6).




Fig. 4.


= Left super.vein 4 Right super. vein : Dorsal aorta wo Suprarenal gland ! . euprarene a » C2 LOE Left kidney gland By Bay bare eee artery Oe cS enal_ vein Ol eine “s \-Umbilical cord Renal vein —— 7 Diverticulum ED Left ureter Meckel x or ! Cy cppendix : Main venous trunk a : Left umbilical art. Right ureter + ANS Rectum R.umbilical art. —p-4 om : ee ae Ischiadica Vena Ischiadica . es L__Femoral artery Arteria femoralis t——Art. Ischiadica Art. Ischiadica Art.Saphena magna 1.


Fig. 5.


Towards the alimentary canal the superior and inferior mesenteric arteries spring from the aorta, but there is no trace of coeliac artery. The superior mesenteric artery, after arising from the aorta, goes directly to Meckel’s diverticulum and sends a branch towards the caecum and appendix. The inferior mesenteric supplies the lower region of the large intestines and gives a big superior haemorrhoidal branch (fig. 7).


We will now describe the return of blood from the body to the umbilical cord. On the left side from above a vessel carries blood from the intercostal spaces and left side of the head end directly to the umbilical cord. See fig. 5. On the right side another vessel carries blood downwards and unites with a transverse vessel from the region of the umbilical ring; it continues downwards and, receiving the right sciatic and femoral veins, goes behind the cloaca in order to join the main vein, which latter is formed by union of the left sciatic and femoral veins from the lower extremity with the vessels of the abdominal and pelvic cavities (renal and mesenteric veins), then the main vein trunk goes towards the umbilical cord.


Fig. 6. Division of dorsal aorta at the level of 5th thoracic vertebra and distribution of vessels near the head end.

Now, following the distribution and positions of the different vessels, we can judge which of them carry blood from the placenta to the body and which carry it back. In the intercostal spaces every branch arising from the dorsal aorta lies between an upper vessel and a lower nerve; the upper vessel does not contain the injection mass. It is a venous vessel and it carries blood towards the placenta.

From the dorsal aorta there are two branches going to each kidney; below the branch to the kidney and between it and the ureter there is a vessel, which by its position and formation in the hylum should take blood from the kidney and carry it to the umbilical cord. It is, I suggest, a renal vein which joins with the main venous trunk (fig. 5). During injection of the main vein we found that the injection mass ran only to the big vessels of the abdominal 76 Boris Boulgakow

cavity and those of the lower extremities; but all the superficial vessels and those which carry blood from the upper part of the body were not injected. Thus we can never imagine that this vessel—main vein—could supply the whole body. On the other hand, on injecting the umbilical artery the injection substance flowed absolutely freely in different directions and filled all peripheral branches and reached every organ and tissue.

Accordingly we can say with certainty that the circulation was flowing in a direction opposite to normal, i.e. through the umbilical arteries to the body and through the veins to the placenta; but these veins should not be called umbilical, but vitelline veins. Probably the circulation was going on through the anastomoses of the umbilical arteries of the monster with the branches of the umbilical artery of the main twin. According to this condition, the heart of the normal twin should be recognised as the propelling agent and the deformed twin is dependent upon the placental circulation of the normal co-twin. The veins of the monster join with branches of the umbilical vein of the normal co-twin in the placenta. F. Schatz in a schematic figure explains the course of the circulation, in this way the vessels of the monster taking origin by anastomoses with the placental vessels of the normal twin (Fig. 8).


Fig. 7.


The umbilical vein itself of the monster did not develop and I suggest that the veins of the monster are the remainder of the omphalo-mesenteric veins. The vessels of the umbilical cord of these monsters are usually defective and communicate with those of the cord of the normal twin. In rare cases, as Keibel points out, the omphalo-mesenteric or vitelline vessels may be found in the cord of the full-time foetus and be seen passing to a persistent umbilical vesicle on the foetal surface of the placenta.



Fig. 8. Placental circulation in a case of acephalus described by F. Schatz.

In a case recorded by Ballantyne four additional vessels were found in the umbilical cord besides normal vessels and they apparently were carrying blood up to the time of birth. In another place he says that “‘the part played by the umbilical vesicle or yolk-sac in the nutrition of the human foetus is apparently not great. At any rate it can only be of use to the foetus in the early weeks of foetal life.” In these early weeks the true yolk-sac therefore is probably a source of supply to the organism in the transition period of neofoetal life, if not later. In another place he writes that in foetuses of other vertebrates, the yolk-sac plays a very important nutritive function, but in mammals it is to all intents of no consequence as a direct source of food supply, although in some mammals it takes part in the nutrition of the foetus. In the Rodentia, Insectivora and Cheiroptera the umbilical vesicle becomes united by its vessels (vitelline or omphalo-mesenteric) with the diplo-trophoblast (Hubrecht) or subzonal membrane plus epiblast, to form a temporary structure connecting the mother with the foetus—the vitelline or omphaloid placenta. I have elsewhere shown reason for supposing that sometimes at least a vitelline placenta may intrude itself into the embryological history of the human foetus, that in the sympodical monstrosity, and possibly in other terata as well, the allantoic vessels do not develop, and yet a placenta is grown, which carries blood to the foetus to the full term of gestation, and that this placenta is formed by the vascularisation of the chorion by the vitelline vessels. 78 Boris Boulgakow

In our case we have apparently evidence of vascularisation of the chorion by the vitelline vessels, due to arrest in development of vessels and they are still not replaced by permanent ones; as evidence of this we have the presence of four vessels in the umbilical cord (two arteries and two veins); persistence of embryonic vessels like arteria and vena ischiadica; and absence of systema venae portae and vena cava inferior. From this we conclude that the embryonic circulation still persists in acardiacus.

It may be that according to Ahfeld’s theory the twins developed from a single ovum and were growing in one sac and the allantois of one twin grew out earlier than that of the other (fig. 9 a), and that the predominant twin obtained a larger area of chorion by attachment of its allantoic vessels. In fig. 9b the allantois of the predominant twin has obtained all the chorion and its vessels are united with the vessels of the monster. In fig. 9 c is shown the circulation, which is already established; the blood from the predominant twin passes through the umbilical artery to the monster.

This forms a good working hypothesis for the origin of the circulation in such monstrosities as acardiacus. It is possible that in consequence of the absence of space in the chorion for attachment of the allantoic vessels of the deformed twin—that the umbilical vein cannot be established directly from the placenta, but the umbilical arteries can join with the vessels of the predominant partner in the placenta itself. In such manner the malformed twin remains alive by getting blood through the placental circulation which is common to both.

If it is assumed that the blood is going to the monster through the umbilical arteries, there ought to be some veins through which blood could be carried away to the placenta; these veins I consider are the remains of embryonic vitelline veins, which join in the placenta.

In conclusion we may say that in our case of holoacardiacus acephalus we have evidence that the blood circulated in an opposite direction to the normal foetus, due to the arrest in development of the embryo at an early stage, when the embryonic vessels had not been replaced by permanent ones,

The Skeleton

The skeleton in this monster consists of the following structures: the vertebral column, the ribs, the scapulae, the clavicles, the episternum, the pelvic bones and bones of the lower extremities. The vertebral column is normal with the exception of the cervical vertebrae, which are fused together into one mass which is bent and appears anterior to the thorax, the spinous processes of this fused mass are flattened and attached to one another. The canal is very narrow. The thoracic vertebrae are well developed and we can distinguish in each vertebra all its constituent parts. The ligaments which join these vertebrae together are well developed and these thoracic vertebrae are joined to the cervical ones by means of the supraspinal ligament. In the lumbar region there are five vertebrae, the lowest of which is slightly deformed. The sacrum is not completely developed and owing to the absence of the spinous processes the canal is left open; the coccyx is represented by a small cartilaginous structure.



Fig. 9a, 6, c. Schematic drawing explaining Ahfeld’s theory of circulation in acardiacus. 80 Boris Boulgakow

In the thoracic and lumbar vertebrae and in the sacrum the primary centres of ossification are present, one in the body and two in the arches.

There are twelve pairs of ribs. Commencing from the 9th rib upwards, the ribs of one side join one another at their sternal ends by means of connective tissue and only in the uppermost part the first rib joins its fellow of the opposite side by means of cartilage. The sternum is not developed; the clavicles are seen directed to the episternum, the cartilaginous structure where the first ribs of opposite sides meet.

All ribs with the exception of the Ist, 11th and 12th have primary centres of ossification.

Keibel says:

The sternal ends of the clavicles become united with one another by a dense band of tissue, which probably represents the episternum of lower forms and later when the heart has descended into the thoracic cavity, the cranial ends of the sternal plates become united with one another, and the episternal band becomes united to them and loses its intimate connection with clavicles.


Of the upper extremities only the scapulae and clavicles are developed and these are cartilaginous A Vi in structure. The scapulae are situated at the level be te of the first two thoracic vertebrae. From the upper . Ap SN and anterior angle of the scapula arises the acromion “Mark Hill (talk) Fig. 10. process, the continuation of which is the clavicle. The skeleton of acardiacus. The vertebral border of scapula is concave, and in the axillary border there is a small incisura which would have been the socket of the humerus; the coracoid is not present. Nearly the same position and outlines of the clavicles and scapulae are described by Keibel in an 11mm. embryo. Compare fig. 11 with fig. 12 taken from Keibel’s Embryology.

The constituent bones of the pelvis are well developed and are normally ossified. In the lower extremities the bones are nearly complete with the exception of some of those of the feet. The two extremities of the femur are fully formed; the shaft of the left femur was fractured accidentally. The shaft is ossified and the secondary centre for the lower end is present. Normally ossification begins in the middle of the shaft at the 7th week of foetal life, but the secondary centre appears during the 9th month. The shafts of the tibia and fibula are ossified. The patella is still cartilaginous. In the left foot the calcaneus, talus, cuboideum, lunatum, and two cunei form bones, three metatarsal bones and five phalanges are present. The 1st and 5th toes are nearly complete; the 2nd toe has only a metatarsal bone with one phalanx. There is a centre of ossification only in the caleaneus. In the metatarsal bones and in the phalanges the shafts are ossified.





Fig. 11. The scapula with acromion, clavicle

Fig. 12. The skeleton of the superior and episternum of acardiacus. extremity in 11 mm. embryo. Keibel.


Fig. 13.


The right foot is less developed; there is one fused cartilaginous mass instead of the talus, calcaneus and cuboid bones; two metatarsal bones for the Ist and 5th toes and two phalanges. The shafts of the two metatarsal bones and the two phalanges are ossified.

Looking at the skeleton as a whole one can see that the bones of the skull are entirely undeveloped; the vertebral column is developed to a certain © extent. The thorax is closed only at the region of union of the first two ribs; the sternum is undeveloped; the upper extremities are represented only by the clavicles and scapulae. All these evidences resemble structures which are seen in the embryo. Besides this, the lower extremities show pes varus, which should be regarded as a congenital abnormality. The limbs are disposed in a natural attitude of flexion in utero and the feet are so placed as to look as if there was pes varus, but there is of course no real club foot. In regard to congenital club foot, this defect very frequently occurs and is associated with ° other malformations. It is due to interference with development, but also may be due to mechanical conditions acting upon the growth of the extremities, such as insufficient room in the uterus or deficiency of amniotic fluid. Pathological conditions which produce these peculiar positions of the lower extremities must be considered, as well as contraction of soft tissues— muscular, tendinous or fascial; or degenerations of bones and joints. Probably these pathological conditions are the result of congenital defect in the central nervous system (absence of brain and degeneration of spinal cord), which caused the muscles, tendons and fasciae not to be developed, being unable to act upon the extremities as usual. This appearance should be regarded not as an arrest of development of the skeleton but as secondary to the mal-development of the above-mentioned tissues. On the other hand, if we examine centres of ossification, we can see that the process of ossification was going on normally, i.e. in those bones, where all primary centres should appear during foetal life, these centres may be seen present, in spite of the degeneration of the spinal cord and the absence of the brain with the pituitary body. Accordingly we suggest that there was no influence of the central nervous system acting upon the growth of bones during foetal life, and the absence of the pituitary body did not prevent the growth.

With reference to the absence of the influence of the central nervous system upon the growth and development of osseous tissue, I wish to allude to the, nourishment of this tissue, which is well developed. It is possible here that the most important réle in the development of osseous tissue was fulfilled by the normal blood supply, regulated by the action of trophic nerves penetrating into the bones together with the vessels. In our case the sympathetic system is present, as we proved by microscopical examination of the suprarenal glands; in these sections the sympathetic ganglia are well developed, and during dissection there were found some nerve fibres, which formed the renal plexus, from which nerves could be seen directed to the vessels. It is well known that when there is injury in the spinal nerves— primary atrophy in bones does not occur, but only secondarily, as a result of the absence of the normal pull of the muscles.

In conclusion, I suggest that the bones increased in size without developing into a complete skeleton, because there was no brain which could regulate development. In our case the skeleton of acardiacus continued to increase in size from the time when development of the embryo was arrested— ‘about 4th—-5th week. Arrest of Development of an Embryo 83

The Thoracic Cavity

The cavity is full of a jelly-like tissue; there was no evidence of any organ (heart, lungs or oesophagus, etc.).

For microscopical examination sections were taken from different places, but everywhere the appearances were the same. In the section is seen connective tissue in an embryonic state with cells and a few capillary vessels. Between thoracic and abdominal cavities there is a septum transversum consisting of fibrous filaments of connective tissue.

Abdominal Cavity

In the abdominal region, 5 cm. above the pubis, is the deficient umbilical ring, through which the umbilical cord is seen passing and some coils of intestines protruding. The subcutaneous tissue of the abdominal wall as elsewhere is oedematous and is blended with the deep fascia and muscles to form one fused mass from which the muscles cannot be separated. Under ff the microscope the muscular fibres were seen to be of the non-striated type and ran in different directions. The subcutaneous nerves are present. Opening of

The coils of intestine, which lie rn reser . “7° penings of in the umbilical aperture, belong to Wojrrign ducts the small and large bowel; this is Opening of Rectum clear from the presence of Meckel’s diverticulum and caecum with appendix. The intestines are covered as a whole with peritoneum and represent one big intestinal loop with the mesentery, which latter goes to the posterior wall of the abdominal cavity. When the abdomina 1 cavity was opened the Fig. 14. Internal structures of the cloaca following structures were found: and urogenital sinus. the small and large intestines with the rectum, the kidneys with the suprarenal glands, genital organs and in the middle the allantois with cloaca to which the rectum is attached. On both sides of the rectum are the ureters in connection with the Wolffian ducts. Stomach, duodenum, liver, pancreas and spleen are wanting. On opening the cloaca one can see by the naked eye the openings of rectum, ureters and Wolffian ducts in the cavity (fig. 14).

Anteriorly the cloaca continues as the sinus urogenitalis (fig. 15), which projects forwards and beneath the pubis like a penis. This latter is 1-5 cm. in length and 11 mm. in thickness and its external aperture is closed by the urogenital membrane. The intestinal tract begins blindly at the level of the 10th thoracic vertebra in the right side. This upper end is distended and its internal surface is folded; this part from its microscopical structure may be considered as jejunum.

Vein from upper part of monster


Fig 15. Schematic drawing of the cloaca of acardiacus showing earlier embryonic stage of development than in Keibel’s model of human embryo from eight and a half to nine weeks old.

In fig. 16 one can see that the wall of the intestine is composed of the epithelium covering the internal surface and the mucous membrane which projects above the surface as the villi. The mucous membrane contains simple vertical gland tubes—the crypts of Lieberkuhn; the mucosal and submucosal muscular layers.


Fig. 16. Section from uppermost part of jejunum.

In spite of the presence of all histological structures, the constituent tissues are not highly developed. Microscopical appearances of the large intestines are normal, but still they are like young tissue. The appendix looks like a continuation of the caecum. All the intestinal tract is 39 cm. in length; Arrest of Development of an Embryo — 85

at a distance of 13-5 cm. from the blind beginning of the small intestine is Meckel’s diverticulum with the superior mesenteric artery, which goes directly to this intestinal part, and at a distance of 18-5 cm. is the caecum. There is no evidence of rotation of the large intestine, and the whole intestinal tube is attached by a primary mesentery. The large intestine ends as the rectum, which latter is ampullated before it joins the cloaca.

On each side of the vertebral column there is a kidney at the level between the 10th thoracic and 2nd lumbar vertebrae, with the suprarenal glands above; the kidneys are brown in colour, deeply lobulated and not of the same size. Left kidney is 2-5 cm. in length, 1-8 cm. in breadth and 0-9 cm. in thickness. The right is 1-9 cm. in length, 1 cm. in breadth and 0-9 cm. in thickness.



Fig. 17. Kidney of acardiacus.

The kidneys are lying under the peritoneum and are covered with capsules containing a lot of fat. The ureters enter the hylum below the vessels; the left ureter descends almost straight, but the right one is slightly sinuous. The kidneys are placed in such a manner that the hylum looks anteriorly. In relation to neighbouring structures the coils of the small intestine are seen lying upon the right kidney; the large intestine rests upon the anterior surface of the left kidney. The lobulation is better marked in the right kidney than in the left. In section the kidney shows the structure of a very young organ with lobules separated by deep interspaces, and each lobule contains a separated pyramid. Peripherally there is a cortical layer overlying a medullary layer. Microscopically one can easily see the well-developed Malpighian corpuscles. The internal wall of Bowman’s capsule is lined with a thin layer of cubical (fig. 17) epithelium, which latter is reflected as cylindrical epithelium to line the external wall of the capsule. Inside the Malpighian corpuscles there is seen the vascular glomerulus, infiltrated with round cells. Uriniferous tubules and collecting tubules may be seen. under the microscope (fig. 17). From the position and structure of the kidneys they appear to be in an early stage of development; this is well shown by Bowman’s capsule, whose external wall in the adult and in the normal child is covered with flat epithelium while the internal wall is like a very thin cuticular layer. Besides, if we compare this with the normal kidney in the adult we find that in our case the uriniferous tubules are only slightly developed and few in number.

The ureters are present at the end of the 4th week of embryonic life as a small bud attached to the Wolffian duct just above its opening into the cloaca. In the 5th week this bud develops a stalk and becomes the permanent kidney and duct (ureter), which lie in the lumbar region.

In conclusion, knowing that the kidneys with ureters are present in the embryo about 4th—5th week and observing the similarity between appearances of a normal embryonic kidney and those in our case, we suggest that there is increase in size of an organ, i.e. growth without corresponding development. Thus here we have arrest of development caused, as I suggest, by absence of a regulating organ—the central nervous system.


Fig. 18. Cross-section though the ovary and remainder of Wolffian body.


Above each kidney there is the suprarenal gland, which under the microscope is seen in the developing stage, but there one can see the zona glomerulosa, fasciculata and reticularis slightly degenerated. Besides these suprarenal structures, there are seen in the section the sympathetic gangliae with big medullary cells.

On each side of the abdominal cavity there is a small organ $cm. in diameter, resembling the ovary. Under the microscope one can easily judge that they are ovaries in an early embryonic stage of development, containing large germinal cells (primitive ova), remainder of Malpighian corpuscles and Wolffian ducts. According to Nagel, at the 5th week it is possible to determine Arrest of Development of an Embryo 87

by microscopical examination whether the genital gland is male or female; if it is to be an ovary the large germinal cells (primitive ova) are numerous and the germinal or coelomic epithelium forms a thick layer of several rows of cells.

In the pelvic cavity there is the allantois which continues upwards as the urachus. The length of these structures is 4-5 cm.; the widest diameter of the allantois is 2-5 cm., its walls are smooth, and the infero-posterior part is thick, forming the cloacal floor. Anteriorly the cloacal cavity continues as a canal (urogenital sinus) below the pubis and it ends blindly, being closed by the urogenital membrane. The length of the urogenital canal, counting from the cloacal cavity, is 4cm.; this canal in its further development is transformed into the urethra and vagina if the future child is to be female. The same state of development of organs in the abdominal and pelvic cavities is described by Ballantyne in his account of a normal embryo in the 4th week.

According to Hertvig, just before the Wolffian duct enters the cloaca, a small blind tube arises from it and is converted into the ureter and kidney. This blind tube appears during the 4th week after impregnation.

All these appearances, as the state of deficient abdominal wall, the protruding intestines with their relation to the peritoneum, the state of cloaca, and the state of development of kidney tissue and genital glands, show that in our case we have arrest of development of an embryo in a very early stage, the organs having increased in size without corresponding development due to the absence of the regulating organ—the central nervous system—and that arrest has taken place about the 4th—5th week after impregnation.

Nervous System

Peripheral nerves. During dissection it was seen that the peripheral nerves were distributed as sensory and motor, and it was recognised that these nerves reached the skin and muscles in all parts which are well developed. Schwalbe mentions that the peripheral nerves are present even if the central nervous system is missing, but these nerves are developed in correlation with de veloping parts.

Microscopical examination of a cross-section of the sciatic nerve shows the following structure: the perineurium as a sheath for the individual nerve bundles; the epineurium, consisting of bundles of connective tissue fibres and containing many vascular trunks cut transversely; nerve fibres composing the nerve bundles are seen as irregular circles which are embedded in endoneurium containing numerous nuclei which belong to the connective tissue cells. The nerves directed to the lower extremities are connected together to form plexuses as usual (the ilio-lumbar, sacral, coccygeal) but before joining the spinal cord they become very attenuated.

Tiedemann in describing a case of acephalus holoacardiacus writes that the nervous system of this monster consisted of the lower part of the spinal cord which began as a ligament in the upper part of the vertebral column. The 88 Boris Boulgakow

lumbar nerves escaped from the spinal cord in a normal condition. The sympathetic nervous system began at the level of the 5th lumbar vertebra and formed the renal plexus with medullary ganglia, from which the nerves were directed to the kidneys.

In our case the main group of sympathetic ganglia is near the suprarenal glands, from where nerve filaments are directed to the kidneys as renal plexuses, and to the vessels.

The Central Nervous System

The central nervous system is very incompletely developed; the brain is absent; in place of the head there is a structure composed of cartilaginous tissue, skin with all adjacent glands and hair, but there is no evidence of nervous tissue. This structure may be called the head of the monster because it seems to be lying on the cervical part of the vertebral column, and besides there are well-developed hairs on its uppermost part.

After removing the vertebral arches and opening the dura mater one can see the spinal cord covered with arachnoid and pia mater. On both sides of the spinal cord there are seen 22 nerve roots and ligamenta denticulata. The length of spinal cord is 10-5 cm.; it begins at the level of the Ist thoracic vertebra, like a ligament composed only of the membranes, and reaches the middle of the body of the 3rd lumbar vertebra, continuing downwards as the filum terminale, which is attached to the end of the sacrum. The nerve roots which arise on both sides of the spinal cord are directed in its upper part upwards, in its middle part horizontally and in the lower downwards (fig. 19).

This evidence shows that the spinal cord stopped development while the vertebral column continued to grow or the spinal cord may have undergone degeneration before it attained complete development. In cross-section the spinal cord appears flattened. Microscopically, a crosssection of the spinal cord taken between two nerve roots at the level of the 5th thoracic vertebra, shows that the central canal is near the anterior surface, and posterior to the canal the medullary substance is degenerated and consists of detritus. The grey matter is not yet differentiated and it is impossible to distinguish it from white matter. Ballantyne says that during the 4th week of embryonic life a beginning is made with the differentiation of the cord into a grey and white part, but as yet there is no contrast in colour, for the medullary sheaths of the nerves yyy. 19. Spinal cord do not appear till the 5th month of antenatal life. of the acardiacus.


Furthermore in our section large cells with outgrowths directed to the - periphery are seen in every part (fig. 20).

According to the above-mentioned facts the central nervous system is in a condition of mal-development (absence of brain and degeneration of spinal cord), thus its influence upon the development of the body was either absent or only functioned to a very slight extent.


Fig. 20. Cross-section through the spinal cord of the acardiacus.

It is known that all parts of the organism are laid down in embryonic life and in future should grow up and take their normal appearance. This applies to the central nervous system as well as all other parts of the body and it completes its development just at the beginning of foetal life; thus if we suggest that it has an influence upon the development of the organism, leading the latter to its complete staté, there should be a connection between it and other parts; therefore if this influence does not exist, all the organs are left to their own efforts for growth and consequently there will be arrest of development. Ballantyne divides the intra-uterine life of the embryo and foetus into the following stages: embryonic period (organogenesis), neo-foetal period, foetal period (growth), neo-natal period and post-natal period (fig. 21). and he says that:

in embryonic life the embryonic physiology has not to do with organs and their special activities, but with the special activity, which produces, builds up, and perfects the organs themselves. The great function of the embryo is to form tissues and organs, or in one word it is organogenesis.

In another place he says:

we have to imagine an aggregate of cells arranging themselves, apparently in a disorderly fashion or in a fashion of which the order is but dimly discerned, first into the three layers of the blastoderm and then after many intermediate stages and phases into the organs which take on the particular functions of foetal and post-natal life. It can be recognised that the principal manifestation of embryonic life stands out prominently as organogenesis, while the chief sign of foetal life is the functional activity of the various organs, which go to constitute the foetal economy. 90 Boris Boulgakow

If this is correct there should be a regulator for the functioning and development of all organs, which I suggest is the central nervous system. If conditions are such as we have in our case, then tissues and organs would only continue in growth with the same appearances in which they were laid down, assuming that there is a good blood supply. The idea that the central nervous system, particularly the spinal cord, is the centre of regulation and formation of all parts of the organism, is not new—it was proposed and supported by many authors (Daresté and others). They tried to prove this by facts; for example, the absence of the olfactory nerves in cyclopia, in which there is often no nose to be found, or the unilateral atrophy of the spinal cord, which leads to congenital absence of one limb Harvey tries to explain hare-lip and cleft-palate or ectopia cordis as evidences of arrest of development. Apart from these facts some embryonic structures persist to a later stage; for example, the aortic arches, or urinary fistula from the persistence of the urachus. Sometimes some structures, which should become rudimentary in the foetal period, remain as malformations by excess as when the Miillerian ducts in the male suffer an arrest in their process of disappearance and are found as Fallopian tubes and uterus in addition to the male genital organs, as for example in hermaphroditus spurius.



t WEEKS Post natal period EveNTS Neonatal period Adaptation

0 P Birth Feotal period Growth 8 , — Neofoetal period 6 Embryonic period qanesis | 0 Post conceptional . Ante - conceptional Impregnation Ovum Maturation | Spermatogenesis Germinial period a Ovum life 6 Sperminal life



Fig. 21.


Of such examples, showing the different evidences of arrest of development, we can give many, but they do not allow us to arrive at a conclusion, because they appear in different kinds of monstrosities and, as Ballantyne says, this explanation, 7.e. the influence of the central nervous system, fails and other modes of origin must be adduced. But if we will examine our monster acephalus holoacardiacus, we can find according to what already has been said above, that there are evidences of arrest in development of all tissues and organs, and that they keep the character of the early embryonic stage before the central nervous system has begun to exercise its control. The objection of Ballantyne, that the presence of many organs and parts in the placental parasite twins (acardiacus) which have no brain or spinal cord seemed to tell against the influence of the central nervous system upon development, does not invalidate my suggestion as to the arrest of development, caused by absence of the brain and degeneration of the spinal cord, because in such monsters as acardiacus, although it is true that many organs are present, as I have proved microscopically, all the tissues and organs are in an embryonic stage and they are only enlarged in size without further development.

Another objection has been raised against the influence of the central nervous system in such monsters as anencephalus, where there is no brain, but the foetal tissues are advanced in development. As many authors suggest, this anencephalic condition may be due to the presence of amniotic adhesions, . or to hydrocephalus, which is the more widely accepted theory. In regard to this theory we find descriptions by Markot, Morgagni, Tiedeman and Ryan, the last of whom writes:

It is easy to understand that the serosity, or water, as it is improperly called, may distend the brain, rupture its membranes, separate the bones of the cranium, burst the scalp and finally escape into the amniotic fluid. The whole brain, membranes, bones and scalp are destroyed by absorption, and the base of the skull alone remains, forming the anencephaly.

In another place he states that: ‘“‘hydrocephalus may advance rapidly, burst the cranium and produce anencephaly or microcephaly.”

J. Y. Simpson states that the malformation in an anencephalic monster arises from disease in intra-uterine life, namely, from bursting of the head when hydrocephalic.

Accepting as a fact that the anencephalic foetus is probably a result of 92 Boris Boulgakow

hydrocephalus, I suggest that anencephalus may take place after the time of embryonic development when all organs have been laid down.

In reference to this Taruffi says that anencephalus cannot take place earlier than the 4th—5th week after impregnation, for the reason that there are often well-formed eyes, but the eyes are not independent of the part of the brain which is destroyed. Alfred W. Hughes (Lancet, 1887) found great difficulties in explaining the fact that eyes with the optic nerves were developed, although only parts forming the posterior vesicle were present, therefore he thought that all the vesicles at one time had been present and underwent a certain degree of development, which afterwards became aborted, and gave place to retrogressive changes.

Thus the presence of well-developed parts of the face in an anencephalic monster does not oppose the fact that the central nervous system must be the regulator during foetal development, because anencephalus may take place during or after the transition period, when the placental circulation is established. If we suggest that anencephalus is due to preceding hydrocephalus, which latter is self-cured by the bursting of the head and escape of the liquid into the amniotic sac, then the remainder of the brain with the spinal cord may take on the control of development. Such a monster can develop and grow because a part of the central nervous system is present and placental circulation is established. Daresté is strongly of opinion that the dominating factor is the defective state of the brain and that the facial and other malformations follow upon this.

Therefore the idea that the arrest of development of an embryo as a whole is a result of absence or destruction of the central nervous system, which should play the role of regulator during foetal life, is quite probable.

Summary

Inthe anencephalic monster, as described above, the brain is absent and the spinal cord is degenerated, therefore there is complete arrest of development due to lack of its influence, but growth without development continues. This is shown in the following facts:

  1. The muscular system has not attained full development and separate muscle fibres are not completely differentiated and no striation can be seen; the appearance resembling smooth muscle fibres.
  2. The blood circulates in an opposite direction to the normal foetus, and embryonic vessels have not been replaced by permanent ones.
  3. The skeleton continues to increase in size from the time when the development of the embryo was arrested at about the 4th to 5th week. In this connection the absence of the pituitary body did not prevent the growth of bones and all centres of ossification are present.
  4. In the thoracic cavity no organs are present; the space being fully occupied by embryonic tissue.
  5. In the abdominal cavity, the stomach, duodenum, liver, pancreas, and spleen are absent; the intestinal canal begins as the jejunum and ends as the rectum opening into the cloaca with the Wolffian ducts and ureters. The — kidneys as well as genital glands show the arrest of development in a very early stage, being increased in size without corresponding development, and in every respect resemble the embryonic organs.

Deductions

  1. This monster belongs to the type anencephalus holoacardiacus (omphaloangiopagus twins). |
  2. The arrest of development of all parts of the organism is a result of absence of the influence of the central nervous system during foetal life.
  3. During the embryonic period all parts of the organism are laid down as well as the central nervous system, but as the latter does not grow further and thus its control is stopped, then the organs and tissues remain in their present state of development and only increase in size.
  4. The development of the bony tissue is not under the control of the central nervous system.
  5. The pathological conditions of the ovum, or the primary injury of an embryo in the early stage of development is a main cause of such malformations as acardiacus.


I would like to thank Professor D. Derry for his great help, guidance and advice. I am indebted to him for revising and correcting the paper, and to Dr A Girgis for helping me in taking photographs and in preparing some microscopical slides.

Literature

(1) KEIBEL, Franz and Matz, FRanciin P. (1912). Human Embryology.

(2) Brrnpaum (1912). The malformations and congenital diseases of the foetus.

(3) BatitantyngE, I. W. (1902). Antenatal pathology and hygiene.

(4) ScHwaLBE, Ernst. Die Morphologie der Missbildungen des Menschen und der Tiere.

(5) AHLFELD (1880). Die Misshildungen des Menschen.

(6) Tarurrt. Storia della teratol.

(7) T1EDEMANN. Anatomie der kopflosen Missgeburt.

(8) GLADSTON, REGINALD J. (1905). “An acardiac foetus.” Journal of Anatomy and Physiology.


Cite this page: Hill, M.A. (2019, October 17) Embryology Paper - Arrest of Development of an Embryo. A Case of Acephalus Holoacardiacus showing Arrest of Development of all Tissues in Embryonic Period. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Paper_-_Arrest_of_Development_of_an_Embryo._A_Case_of_Acephalus_Holoacardiacus_showing_Arrest_of_Development_of_all_Tissues_in_Embryonic_Period

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