Paper - On the development and shape of uriniferous tubules of certain of the higher mammals (1905)

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Huber GC. On the development and shape of uriniferous tubules of certain of the higher mammals. (1905) Amer. J Anat. 4(Suppl.): 1-98.

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This historic 1905 paper by Huber is an early description of the development of the renal nephron, "uriniferous tubules" in several species (human, rabbit and pig.


Note portions of this paper's text were displayed in a smaller font as unnumbered footnotes or representing a more detailed aside description. The online version has not yet applied different formatting to these text sections.


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On the Development and Shape of Uriniferous Tubules of Certain of the Higher Mammals

G. Carl Huber

By G. Carl Huber

From the Histological Laboratory of the University of Michigan.

With 24 Figures.

Introduction

As is well known, the excretory system of the amniota develops as a series of distinct organs, the pronephros, the mesonephros, and the metanephros. The pronephros, which is the first excretory organ to differentiate, and is also phylogenetically the oldest, disappears in all amniota; its consideration is here dispensed with. The mesonephros, which functionates throughout life as the chief excretory organ of anamnia, is an embryonic organ in amniota, in which it disappears as an excretory organ and is replaced by the permanent or true kidney, the metanephros. The development of the metanephros is, however, so closely related to that of the mesonephros, in both its phylogeny and ontogeny, that a consideration of the development of the former will to some extent necessitate a consideration of the development of the latter. This will be done only so far as necessary, as a consideration of the development of the mesonephros will not form a part of this contribution.


Our present day conception of the anlage and development of the metanephros dates from Kupffer’s contribution based on observations made on sheep embryos. In an embryo 8 mm. in length he found that from the dorsal wall of the Wolffian or mesonephric ducts near their posterior termination, there is formed an evagination which he designated as the “ Nierenkanal.” These buds, one of which appears in connection with each Wolffian duct, grow dorsally and cephalad and, as observations on older embryos revealed, become associated with the development of the permanent kidney. Anticipating these observations, we find those of Remak and Kélliker, who recognized these buds, but traced their origin to the cloaca or bladder, and of still earlier date the observations of Rathke, who recognized a blastema situated between the dorsal wall of the embryo and the mesonephros in which the kidney had its origin and from which the ureters were supposed to grow toward the bladder. That the permanent kidneys have their origin from buds which arise from the Wolffian ducts is now very generally accepted, Kupffer’s observations having been widely confirmed and extended to embrace the different classes of the amniota. While, as just stated, there is a unanimity of views concerning the anlage of the permanent kidney, the views concerning the mode of development and the histogenesis of the tubular and other structural elements are still at variance.


According to Remak and somewhat later Kolliker, the development of the permanent kidneys, after their anlage in the buds arising from the Wolffian ducts, proceeds in a manner similar to that observed for other tubular and for alveolar glands, or, as stated by these observers, after the manner of the development of the lungs. The epithelial kidney anlage was said to grow forward and to present an anterior vesicular enlargement, which soon elongates, the anlage differentiating into ureter and primitive kidney pelvis. On this, solid buds and ampulle make their appearance, which in their further growth enlarge and elongate and obtain a lumen, thus forming anlagen for the papillary ducts. These in their further growth undergo division and give origin to hollow buds which form the anlagen for the convoluted (secretory) portions of the uriniferous tubules and the epithelial portions of the Malpighian corpuscles. According to this view the collecting ducts and coiled uriniferous tubules are developed by direct budding from the epithelial renal anlage derived from the Wolffian duct.


On the other hand, Kupffer described a discontinuous origin for the uriniferous tubules: In a sheep embryo of 10 mm. length, he observed a group of cells, clearly differentiated from the surrounding tissue and in close relation with the renal anlage—Nierenkanal—in which he recognized the anlage of the kidney (figured in Fig. 4, Pl. XV of his article). In this group of cells Kupffer recognized three zones—a zone consisting of compactly arranged cells in close relation to the renal anlage; a middle zone of less compactly arranged cells, and an outer zone in which connective tissue fibers were observed. In a sheep embryo of 15 mm. length, a differentiation in the middle zone was observed in that the cells were arranged in twisted cords (“Zellen sich in gewundene Streifen ordnen”) which were as yet not clearly differentiated. The cells of these twisted cords were not connected with the renal anlagen. These cords were interpreted as the anlagen of the coiled uriniferous tubules. The darker zone of cells immediately surrounding the renal anlage was thought to contribute to their further development. Kupffer could not exclude the possibility that perhaps later generations of tubules had an origin which differed from that here given this view, the coiled uriniferous tubules have their origin in a tissue which is distinct from that of the renal anlage. Kupffer’s observations though faulty in many respects, as later investigations have shown, must be recognized as of fundamental importance, as concerns both the phylogenetic and the ontogenetic development of the permanent kidney.


Nearly all investigators who, since the appearance of Kupffer’s observations, have considered the question under discussion, have adopted one or the other of the two views above hastily sketched and, even taking into consideration the most recent contributions to this subject, the statement seems warranted that the problem under discussion is still awaiting final solution. Schreiner, in a recent most admirable contribution to this subject, especially as concerns the earliest stages of the development of the permanent kidney, has grouped under respective heads all the more important contributions dealing directly or indirectly with the development of the permanent kidney, and, as it is not my purpose to enter extensively into a discussion of all the literature bearing on the topic under consideration since this has been undertaken by Riickert, Herring and Schreiner, I have adopted and extended the above mentioned classification of Schreiner. So far as accessible to me (the exceptions I have noted), I have critically reviewed the literature to which reference is here made. It should, however, be stated that, while adopting such a classification, I must regard it as somewhat forced. A number of the contributions here referred to and especially certain of the earlier ones, require interpretation through a view-point gained by familiarity with more recent investigations and with actual preparations before a classification of them can be made.


Among investigators who adhere to the view that the tubules of the permanent kidney are developed by a direct budding from the epithelial renal anlage derived from the Wolffian duct after the manner of other tubular and of alveolar glands may be mentioned :—Remak, 55; Kélliker, 61; Colberg, 63; Waldeyer, 70; Toldt, 74; Pye, 75; Lowe, 79; Ribbert, 80; Hortolés, 81; Kallay, 85; Janosik, 85; Nagel, 89; Golgi, 89; Minot, 92; Haycraft, 95; Schultze, 97; Kollmann, 98; V. Ebner, 99; Gerhardt, o1; Stoerk, or; Strahl, 02; Disse, 02; Stoerk, 04. Stoerk’s fuller publication gives no additional data as to his view of the origin of the uriniferous tubules and I assume that he still adheres to the views expressed in his earlier contribution.


The investigators who have followed Kupffer in assuming a separate and distinct origin for the coiled uriniferous tubules may be arranged as follows:

Bornhaupt, 67; Thayssen, 73; Riedel, 74; Balfour, 76; Braun, 78; Fiirbringer, 78; Emery, 83; Wiedersheim, 90; Hamburger, 90; Weber, 97; Chievitz, 97; Ribbert, 99; Herring, 00; Schreiner, 02; Haugh, 03; Keibel, 03; Felix, 04. These observers, while expressing a unanimity of view concerning the separate anlage of the tubular system of the permanent kidney, are not in accord as to the histogenesis of the tissue from which the tubules are differentiated.


Certain observers, among whom may be mentioned Sedgewick, 80; Riede, 87; Hoffmann, 89; Gregory, 00, may be separately grouped, since they assume an intermediate position inclining toward a separate anlage of the tubules but assuming a histogenetic relationship between the tissue from which the tubules are developed and the epithelial renal anlage. This brief array of the contributors to the literature under consideration may serve as an introduction to a fuller discussion of certain of the more recent contributions; these and others will receive further mention in presenting the results of my own investigations.


Of the recent contributions to our knowledge of the development of the permanent kidney, the article of Schreiner deserves special mention. The results presented are based on observations made on representatives from the different classes of amniota and embrace a study of the origin and development of the tubules of the Wolffian body and of the anlage of the different constituent elements of the permanent kidney. I find it somewhat difficult to give a brief summary of this article, which is accompanied by numerous illustrations of sections, of profile reconstructions and of reconstructions after the Born method. The discussion of his own observations, he begins for each type investigated with a consideration of the histogenesis of the tubules of the Wolffian body, following this by a discussion of the origin and development of the permanent kidney in each type. Schreiner traces the origin of the tubules of the Wolffian body to a cell-mass which he designates as the nephrogenic tissue (a term suggested by Rabl), which is identical with the blastema of other authors. This nephrogenic tissue has its origin in the intermediate cell-mass and extends as an unsegmented cord along the mesial and dorso-mesial side of the Wolffian ducts to their termination in the cloaca. From the ceils of this cord of cells, which increase in number by division, are differentiated the tubules of the Wolffian body. These appear first in the anterior segments and, as development proceeds, also in the posterior segments. The differentiation of the tubules of the Wolffian body does not, however, extend to the posterior limits of the nephrogenic tissue, but ceases a number of segments anterior to the termination of the Wolffian duets and nephrogenic tissue. The permanent kidneys have their origin in evaginations (one for each side) from the dorso-mesial wall of the Wolffian ducts not far from their termination in the cloaca. These evaginations grow dorsally into the posterior portion of the nephrogenic tissue and in doing so become capped with the nephrogenic tissue. The evaginations, or as they are known, the renal anlagen, rena) ducts or Nierenginge, at first present a bulbous extremity. This elongates in an antero-posterior direction and develops buds and ampulle. In the meantime, the nephrogenic tissue, which at first surrounds the bulbous extremity of the renal anlagen as a compact cell-mass, breaks up into several cell-masses, each of which caps one of the primary branches of the renal anlagen, at the same time losing its connection with the nephrogenic tissue from which are developed the tubules of the Wolffian body. This portion of the nephrogenic tissue Schreiner now terms the metanephrogenic tissue in contradistinction to the mesonephrogenic tissue. The metanephrogenic tissue, in the majority of the forms studied by Schreiner may be differentiated more or less clearly into an inner zone composed of eells more compactly arranged and presenting other characteristic features and an outer zone, the cells of which are less compactly arranged and approach in appearance mesenchymal tissue. Schreiner further shows that the epithelium of the ureters and pelvis of the kidney as also the collecting tubules to their terminations are developed from the rena] anlagen (Nierengiinge), while the secretory portion of the uriniferous tubules from their termination in the collecting tubes to and including the epithelial portion of Bowman’s capsule are differentiated from the inner zone of the metanephrogenic tissue, the interstitial tissue and the capsule of the kidney developing from the outer zone. Schrejiner’s observations, accompanied by a very full discussion of the Hterature and substantiated by numerous figures, appear to argue conclusively for a separate anlage of the tubules of the Wolffian body and the secretory portion of the uriniferous tubules. I regard it as a distinct achievement on his part to be able to trace the close relationship between the mesonephrogenic tissue from which are developed the mesonephric tubules, the separate anlage of which is generally accepted, and the metanephrogenic tissue from which are developed the secretory portions of the uriniferous tubules of the permanent kidney. As is no doubt evident, the nephrogenic tissue here referred to has long been known as the renal blastema : there are, however, various opinions regarding its origin and its share in the development of the kidney. I shall have occasion to make further reference to this excellent article of Schreiner.


Herring, in a very creditable contribution based on observations made on material derived from human embryos, was first led to believe that the kidney tubules were branches of the collecting tubes, but “could never find the early stages, which should have been easily seen if that view were correct.” He further states that “in the thick layer of the capsule, cells are seen which show a gradual transition in appearance from embryonic connective tissue cells to a character resembling that of the epithelial cells of the early convoluted tubules. Between these cells and those of the ampulle” (dilated ends of the collecting tubes) “ there is always a distinct line of separation and in the majority of instances there is a space where the tubule has shrunk during the process of hardening. The careful examination of serial sections has convinced me that these masses of cells which appear under the capsule and in the interlobular septa, are quite independent of the ureter branches and give rise to the Malpighian bodies, convoluted tubules‘and Henle’s loop, uniting always with short branches from the ampulle.”


Hamburger’s paper, based largely on investigations made on the kidneys of mouse embryos and young mice, contains important data concerning the later stages of the development of the uriniferous tubules and the development of the Malpighian pyramid. His observations are based on serial sections and on what must be regarded as very successful preparations made by maceration and teasing. He makes only incidental mention of the origin of the uriniferous tubules, which he regards as developing from small bodies {(Kérperchen), the smallest of which are spherical cell groups which have only an apparent connection with the enlarged distal ends of the collecting ducts.


Haugh, in one of the most recent contributions to the subject, in which he presents observations made on an extensive material derived from human embryos of all ages, gives a full account of the development of the pelvis of the kidney and of the shape of the pelvis of embryonic and adult kidneys, based on metal injections and on wax reconstructions. He also presents data concerning the lobulation of the human kidney and on the development of the collecting tubules. He treats, however, very superficially—to use his own words—the earlier stages of the development of the uriniferous tubules, allying himself with those authors who defend a separate anlage of the uriniferous tubules.


Stoerk, on the other hand, defends the older view of the development of the uriniferous tubules. According to this observer, the renal anlage, derived from the Wolffian duct, grows dorsally and, after repeated dichotomous division, meets the anlage of the renal capsule which retards the further radial growth of the tree-like branches of the renal anlage. Each of the branches now develops an ampullar enlargement at its extremity, which later assumes a heart-shape. Each half of the heart-shaped enlargement buds out laterally and forms a short tube, the whole structure now assuming the appearance of a Y. Each arm of the Y-shaped termination then divides dichotomously, the one branch, which for a time remains small, passing toward the periphery, the other, which grows more rapidly, budding and growing toward the stem of the Y. The Y-shaped structure now presents the appearance of an inverted anchor. The points of this anchor-shaped structure now grow in such a manner as to assume the shape of an S. Such an S-shaped structure is an anlage of a uriniferous tubule and of Bowman’s capsule. Stoerk’s more recent contribution contains only a brief statement concerning the anlagen and early developmental stages of the uriniferous tubules and this is merely a reiteration of the views presented in his earlier paper. In this second paper, Stoerk gives the results of observations made on serial sections of material derived from human embryos and numerous wax-reconstructions made therefrom. These reconstructions represent mainly the earlier developmental stages of the uriniferous tubules, a fact which is no doubt responsible for certain errors which he has committed, in using the data gained by a study of the earlier stages to interpret the shape and structure of more fully developed tubules. As I shall have occasion to refer frequently to this paper in connection with a discussion of my own results, its further consideration may here be dispensed with Gerhardt, who has recently published, from O. Hertwig’s laboratory, also defends the view that the uriniferous tubules are developed by budding and that the permanent kidney is an organ sui generis. As material, he used largely mouse embryos, but also those of chicken, dog, and pig. Gerhardt’s article is concerned largely with a discussion of the Hterature and with theoretic speculations. His own observations are very briefiy given and, as illustrations are wanting, may be summarized by giving one of his conclusions: ‘‘ The peripheral portions of the uriniferous tubules arise through a continuous growth of the collecting tubes. It cannot be demonstrated that in the cortex formed tubes make secondary connection with the tubules of the medulla.’ The capsule of the glomeruli he regards as an invagination of the distal end of the uriniferous tubules.


In Chapter IV (Entwickelungsgeschichte und Missbildungen der Nieren) of Vol. 52b, Deutsche Chirurgie (Kiister, Krankheiten der Niere), written by Strahl, this observer states that so far as his own observations go, he is inclined to accept a continuous epithelial anlage of the uriniferous tubules as given by Minot and Nagel; he does not, however, desire to commit himself until he himself has made further investigations. A number of excellent illustrations are found in this chapter.


Disse, who discusses briefly the development of the kidney in his account of the anatomy of the urinary organs as given in Bardeleben’s Handbuch, states that as a result of his own observations made on guinea pig and pig embryos, he is Jed to conclude that both the straight and the coiled uriniferous tubules have the same anlage, namely from the hollow buds of the primitive kidney pelvis. The selection of the section which forms the basis for his Fig. 77, showing the anlage of the coiled uriniferous tubule seems to me unfortunate. The S-shaped portion (anlage of the coiled tubule) is not cut through the center of its lumen, only a small part of which is seen in the figure. The apparently continuous structure as represented might, it seems to me, be simulated by an overlapping of the two bevelled surfaces of two discontinuous structures (anlage of coiled tubule and collecting duct), especially as the section from which the drawing was made seems to have been relatively thick.


Haycraft’s contribution to the development of the kidney of the rabbit may yet receive consideration as his observations have been widely accepted. He states that ‘‘the tubules and Malpighian bodies arise as buds of solid cells from the wall of the primary renal vesicles”? (ampullar enlargement of the primary divisions of the renal anlage) ‘‘close to the cortex. The bud makes a double bend like an S, first turning with a large sweep away from the vesicle, then turning toward it and sharply away again. The basement membrane can be traced along it and a central lumen forms almost to its tip.’ Haycraft also traces the development of these S-shaped buds into the uriniferous tubules and gives his conception of the form of such a tubule as present in the adult kidney of rabbits. The figures accompanying this article are of special interest to me, since my series of sections of rabbit embryos of various ages as also numerous reconstructions of uriniferous tubules made from the same, afford a basis for their interpretation. His Fig. 8, ‘“‘A high power view of the first formation of a urinary tubule from a primary renal vesicle’? represents, I fear, a much older stage, only a portion of this tubule being shown in the section sketched. His Fig. 10, I interpret as embracing parts of at least two tubular anlagen, there sketched as one tube, owing to the position given to the glomerular anlage with reference to the other portions of the tube. Further reference to this article will be made later.


Brief mention may yet be made of the conclusions reached by a number of observers who have investigated the development of cystic kidneys. Hildebrand suggested that the want of union between the collecting tubules and the anlagen of the uriniferous tubules was the cause of the cysts of the congenital cystic kidney, in that, when this condition obtains, as “the glomeruli begin to functionate there is no opportunity for the outflow of the secretion and consequently the tubules are expanded into cystic structures.” Ribbert, who describes observations made on a cystic kidney of a new-born male child, was able to show that many of the cysts were developed from Malpighian corpuscles which showed no connection with collecting tubules, the ends of certain of which were also cystically enlarged. Meyer found in microscopic sections of the kidneys obtained from a 9-weeks-old female child, which showed other congenital defects, certain regions where the kidney parenchyma was normally developed and other regions where collecting tubules and Malpighian corpuscles were observed, but where the tubular portions of the uriniferous tubules which normally unite these structures are wanting and in place of which there was observed ‘‘an undifferentiated tissue rich in cellular elements in which the cells only in certain regions were arranged in the form of rings or cords.” These observations, it appears to me, confirm in a satisfactory way the conclusions of observers, who recognize separate anlagen for the collecting tubules and the uriniferous tubules proper.


From this brief summary of the literature, it may be seen that the controversy found in the early literature concerning the origin and development of the coiled portion of uriniferous tubules of the permanent kidney is still found in the more recent literature, the weight of evidence, however, being on the side of a discontinuous origin of the coiled portion of the tubule, as Felix has very recently correctly stated.


This investigation was begun in the spring of 1902. In considering the possible sources of error of other investigators who have dealt with this subject, it occurred to me that the thickness of the sections studied might alone be responsible for a certain per cent of the discrepancies found in the literature. The average thickness of serial sections of embryos used in embryological investigations is seldom below 10 p», more often perhaps 20 ». My own observations soon convinced me that sections having a thickness of 10 to 20 » were not suitable for interpreting the early stages of kidney development, as in some sections fields were found which might be used respectively for demonstrating either a continuous or discontinuous origin of the coiled uriniferous tubules. It was further hoped that a solution of the question might be obtained by making free use of reconstruction methods, especially of the Born wax-plate method. The wax-plate method of reconstruction had previously been used in the study of the development of the kidney by Chievitz. He gives three figures, which are, however, somewhat difficult to interpret, owing to the fact that the models were not completed by smoothing over the irregularities which always result when the cut-out portions are placed together. Since my own investigation was begun and in part completed, there have appeared three contributions based in part or as a whole on data gained by reconstructions. Mention has been made of the work of Schreiner, who, however, studied, among other questions, only the anlage of the coiled tubules and of this portion of his work he gives no reconstructions. Haugh’s reconstructions are confined almost wholly to such of the pelvis and straight collecting tubules of kidneys of relatively young human embryos. It is rather to be regretted that Haugh did not devote more time to the finishing of his wax models, which would have enabled him to give clearer illustrations of the models made, than accompanying his otherwise excellent article. The most recent contribution to this subject, that of Stoerk, is based largely on results obtained by means of wax-plate reconstructions, the value of which method he clearly recognizes. The contributions of Schreiner, Haugh, and Stoerk which, as stated, have appeared since my own work was in progress, have been. of material assistance to me in formulating my own views. They do not, however, as appears to me, make superfluous the publication of my own results. These are confirmatory, as will appear, of that portion of Schreiner’s work which deals with the anlage of the metanephros and its tubules; Haugh touches only incidentally on the development of the coiled uriniferous tubules ; and finally my own observations have led me to conclusions which differ materially in a number of particulars from those reached by Stoerk.


The investigation, as projected, included not only a study of the anlage of the uriniferous tubules and their mode of development, but also a study of the form of the more fully developed uriniferous tubule, if possible by means of wax-plate reconstruction. That this seemed desirable, requires, I believe, no argument. A portion of the results here given were presented at the December meeting of the Association of American Anatomists in 1903, accompanied by a demonstration of a portion of the models here figured.

Material

In selecting the material to be used, it seemed to me desirable to include in this study developmental stages of both simple and lobulate kidneys; the embryos selected depended largely on the accessibility of the material. The embryological material used in the investigation was as follows:


Human Embryos
Number Length or Age of Embryo Fixation Remarks
1 About 15 days old Formalin Received from Dr. Chivers of Jack., Mich. (Not well preserved).
2 10-mm. neck-breech Alcohol Received from Dr. Steiner of Lima, Ohio.
3 15-mm. neck-breech Miiller’s fluid Received from Dr, Roberts, Buffalo, N. Y.
4 18-mm. head-breech Formalin Received from Dr. Peterson, Ann Arbor.
5 20-mm. head-breech Formalin Received from Dr. Peterson, Ann Arbor. Model, Fig. 1(B)
6 22-mm. head-breech Formalin
? 3-em. head-breech Formalin Received from Dr. Hickey, Model, Fig. 9.
8 4-cm. head-breech Formalin Received from Dr. Hickey.
9 5.8-cm. head-breech Formalin
10 6-cm. head-breech Mullers fluid
11 6.5-em. head-breech Formalin Received from Dr. Hickey, Model, Fig. 10.
12 18-cm. head-breech Formalin Received from Dr. F. C. Wright, then of Calumet, Mich.
13 14.5-em. head-breech Formalin Received from Dr. Darling, Ann Arbor.
14 14.5-cm, head-breech Formalin Received of Dr. F. C. Wright, then of Calumet, Mich.
15 18.5-cm. head-breech Formalin Received of Dr. F. C. Wright, then of Calumet, Mich.
16 Early part of 7th mo. Bichloride Dr. Warthin, Ann Arbor, only the kidneys obtained. Models, Fig. 4.
17 27 cm. in Length Zenker’s and Orth’s Dr, C. 8. Minot, Boston. Only fluids the kidneys available.
18 Child less than week Formalin
19 Child 10 days old Bichloride
cat Embryos
Number Length or Age of Embryo Fixation Remarks
1 9-mm. neck-breech Bichloride
2 13-mm. head-breech Bichloride Model, Fig. 1 (A).
3 20-mm. head-breech Muller’s fluid
4 22-mm. head-breech Bichloride Models, Fig. 6.
5 3-cm. head-breech Formalin sees cece ee Sette enone
6 4-cm. head-breech Formalin Model, Fig. 16 (A).
7 4.5-em. head-breech Formalin
8 6-cm. head-breech Formalin Model, Fig. 16 (B).
9 9-10-cm. head-breech estimated as just before birth Zenker’s fluid Models, Fig. 18 (A) and Fig. 20.
10 Kitten 1 month old Zenker’s and Tellyesmicky’s fluids
12 Kitten 214 months Zenker’s and Tellyeold snicky’s fluids
14 Full grown cat Zenker’s and Tellyesnicky’s fluids
rabbit Embryos
Number Length or Age of Embryo Fixation Remarks
1 9-mm. neck-breech Bichloride
2 14-mm. head-breech Zenker’s Fluid Models, Fig. 5, A, E, F.
3 18-mm, head-breech Bichloride Models, Fig. 5, B, C, D.
4 20-mm. head-breech Tellyesnicky’s fluid
6 22-mm. head-breech Alcohol-acetic
7 29-mm. head-breech Alcohol-chloroform acetic
8 3.5-cm. head-breech Zenker’s fluid Models, Fig. 14.
9 4-cm. head-breech Zenker’s fluid
10 4.3-em. head-breech Tellyesnicky’s fluid
11 4.5-em. head-breech Muller’s fluid
12 4.8-em. head-breech Formalin
13 6.5-cm. head-breech Formalin Models, Fig. 18 (B) and Fig. 19 (A).
14 Rabbit one day old Zenker’s fluid Model, Fig. 19 (B).
pig Embryos
Number Length or Age of Embryo Fixation Remarks
1 5-mm. neck-breech Sublimate-acetic
2 10-mm. neck-breech Sublimate-acetic
3 14-mm. neck-breech Chromic acid
4 18-mm. head-breech Graaf’s fluid
5 20-mm. head-breech Picro-sulphuric
6 28-mm. head-breech Chromic acid
7 24-mm. head-breech Alcohol-acetic Model, Fig. 17, B.
8 28-mm. head-breech Formalin Models, Fig. 17, A and C.
9 3-cm. head-breech Formalin
10 3.5-cm. head-breech Formalin
11 4.4-cm. head-breech Formalin
12 5-cm. head-breech Formalin

Method

Of the various fixing fluids used, fixation by Zenker’s fluid proved most satisfactory.

The wax-plate reconstruction method was largely used in gaining the data which form the basis for this contribution. It was found that the material could be most readily manipulated in this way by using serial sections 5 » in thickness and a magnification of 400 diameters, necessitating the use of wax-plates 2 mm. in thickness. As already stated, it is often exceedingly difficult in sections more than 5 y in thickness to interpret with any degree of clearness the earlier stages in the development of the kidney tubules; the same may be said of sections from more fully developed kidneys, where the tubules are already well differentiated. The difficulty here met with is that even in sections having a thickness of not more than 10 p, the tracing of a tubule through a series of sections is often made difficult by the fact that portions of two tubules lying over each other—with reference to the plane of the section—and in contact are both included in the same section and appear as one tubule, thus easily leading the observer astray. For the earlier stages—embryos having a length of about 1.5 cm.—the entire embryo was cut in sagittal serial sections; for embryos measuring from 1.5 to 2.5 em., only the posterior half was thus cut, and for older stages, the kidneys were removed after fixation and cut in series either longitudinally or transversely. The difficulty of obtaining unbroken series of sections 5 in thickness, without wrinkling or distortion when mounted, was met for many of the series by cutting the sections one by one on an ordinary sliding microtome—Altmann pattern—with the knife at an angle of about 45° and with the knife blade covered with a layer of distilled water while cutting. This latter procedure I have found very useful in cutting thin paraffin sections. The sections are transferred as cut to an Esmarch dish filled with distilled water in which they float and flatten out. They are arranged as cut on a slide covered with albumin fixative placed at an angle in the same dish. When the slide has been filled with sections, it is placed on the warm oven until the water evaporates. The sections are then ready for staining. This procedure, though much more timeconsuming than when the sections are cut with an automatic microtome, seemed to present advantages which compensated for the additional time necessary for its prosecution ; especially was this true for the older stages, in which the kidneys alone were cut. The sections were stained on the slide in Ehrlich’s hematoxylin and counterstained mainly in eosin or erythrosin, the latter giving the better differentiation and sharper contrast than the other protoplasmic stains used.


The outline drawings used in making the models were sketched with the aid of the camera lucida, a comparatively easy procedure for the earlier stages, very time-consuming for the later stages, where constant shifting of the field was necessary. The steps used in making the models were those generally used when the Born wax-plate method of reconstruction is employed. Special orienting planes or lines were generally dispensed with, as it was found practicable to use for this purpose certain prominent structures within the sections. The reconstruction of the earlier stages of kidney development—the primary renal anlage and renal pelvis with its primary branches, also the earliest developmental stages of the uriniferous tubules—is a comparatively simple procedure. The same can, however, not be said of the older stages and more fully developed tubules. The complicated and varied arrangement of the proximal and distal convoluted portions of the more fully developed uriniferous tubules, above all the length of the loop of Henle make the tracing of a single tubule through a series of sections a matter of difficulty. However, on careful search through a series of sections, instances would be found where one or the other arm of Henle’s loop was cut through nearly its entire length. By using this as a starting point, it was generally possible to trace the remainder of the respective tubule. In doing so, it was found helpful to make profile or temporary wax reconstructions of certain parts of the tubule or to make temporary reconstructions of all the tubules of a given area supposed to contain the portions of the tubule sought and in this way separate it from surrounding tubules. After thus mapping out a given tubule in its entirety, drawings were made which could be used for reconstruction of the whole tubule.

Anlage and Early Stages of Development of the Metanephros

The earlier stages of the development of the permanent kidney, the anlage and early development stages of the renal evagination and of the nephrogenic tissue (kidney blastema) shall here be considered very briefly, since the appearance of Schreiner’s contribution obviates the necessity of a fuller discussion of this portion of my investigation. Neither does it seem necessary to reproduce by way of illustrations the numerous models made in the earlier part of this work showing shape, size, and relationship of the renal evagination as found in the cat, rabbit, pig, and man, nor to discuss the appearances presented by them during the earlier developmental stages, since such figures would in nearly every instance duplicate the figures of similar stages given by Schreiner (rabbit, text-figure 15-21; human, text-figure 26-27 ; pig, text-figure 29-30 of his article) based on profile and wax reconstructions, except for the cat; this animal he did not study, but it presents no special features. Schreiner considers very fully the anlage and early developmental stages of the kidney of the rabbit. A brief review of his account may here be given. In the rabbit, the renal evagination arises in the 31st segment (about the 11th day, Kolliker, Minot) from the dorso-median wall of the Wolffian duct near its termination in the cloaca and grows into a tissue known as the nephrogenic tissue, which soon surrounds its blind end as a cap of hemispheric shape. As concerns the renal evagination, Schreiner’s and my own observations confirm those of other investigators, who, since the appearance of Kupffer’s contribution, have studied the anlage of the kidney in amniota. Opinions differ, however, as concerns the histogenesis of the tissue generally known as the renal blastema here designated as the nephrogenic tissue and as to the réle it plays in the development of the kidney. The general statement may be made that observers who regard the kidney tubules as developing by a process of budding, interpret the nephrogenic tissue as of mesenchymal origin, destined to form the capsule, interstitial connective tissue and vascular sheaths. Concerning it Minot states that “the histogenesis of the mesenchymal portion of the kidney is almost unknown.” The majority of those observers who accept a separate origin for the kidney tubules have traced their origin to a special tissue (nephrogenic tissue, renal blastema) the histogenesis of which may here be considered, although in doing so it will be necessary to anticipate certain facts which will be considered more fully later. This seems justified, since the tissue in question makes its appearance before the renal evaginations are present.


Braun, in his account of the development of the urogenital system of reptiles (lizards), described irregular cords of cells (Nierenzellenstrang, generally known as Brauns cords), whose origin he traced to the celomic epithelium and which were thought to be the anlage of the uriniferous tubules. Minot regards these cords ‘‘as merely the beginning of the condensed mesenchyma of the renal anlagen,” and Schreiner regards them as identical with the cell-mass designated by him as nephrogenic tissue. Wledersheim, in his account of the development of the urogenital apparatus of crocodile and turtle embryos, confirms in part Braun's observations, di ering from him in that he regards the caudal end of the mesonephros as the seat of origin of the cellmasses or cords from which the kidney tubules are developed. He recognizes further a condensed mesenchyme which surrounds the metanephric duct and which he characterizes as staining more deeply than the surrounding mesenchyme with which it plends. This proliferating cell-mass, which, as he states, is also found in other amniot embryos can not alone be regarded as the ‘‘metanephros blastema,” as it in itself does not give origin to the strictly glandular parts of the kidney, but the interstitial connective tissue and the vessel sheaths. Sedgewick, who gave a very clear account of the anlage of the mesonephros and metanephros as observed in chick embryos, traces the origin of the Wolffian tubules to a cell-mass designated by him the Wolffian blastema, which has its origin in the intermediate cell-mass. As described by him, the Wolffian blastema extends as far back as the 34th segment, that is, to the opening of the Wolftian duct into the cloaca. This Wolffian blastema breaks up into the Wolffian tubules as far back as the 30th segment. He states further that “ behind this point it remains for some time almost or quite passive and ultimately gives rise to the epithelium of the permanent kidneys. In consequence of this, I have called that part of the Wolffian blastema between the 31st and 34th segments the kidney blastema,” and again “ that it is important to notice that this kidney blastema develops in exactly similar manner to the Wolffian blastema. It is not until the fourth day, when the ureters have appeared that it is possible to draw a line between the two.” “In yet older embryos, {n which the ureter is more fully developed and overlaps the hind end of the Wolffian body, the kidney blastema has quite broken off from the Wolffian body and invests the anterior end of the ureter.” have quoted thus fully from Sedgewick’s paper, because he is the first to give a clear account of the histogenesis of the tissue into which grows the renal evagination. Ribbert, in a recent contribution, also discusses the origin of the tissue (which he characterizes as a differentiated cell-layer), which surrounds the blind end of the epithelial renal anlage, put gives no definite conclusions. Certain it is, he states, at the ureters grow into a dense cell-cord, which may be regarded as the distal end of the mesonephros, as is shown in his Fig. 4, combined from three sections of a series of sections of a Guinea-pig embryo. The histogenesis of the nephrogenic tissue (renal blastema) has been very fully considered by Schreiner, as has been stated in a brief review of his work given on page 4. For all types.studied by him, he was able to show very conclusively that the nephrogenic tissue of the metanephros in common with that of the mesonephros had its origin in the intermediate cell-mass and extended as an unsegmented cord of cells through the regions in which is developed the mesonephros to where the Wolffian duct terminates in the cloaca. In the region of the mesonephros, this tissue gives origin to the mesonephric tubules; posterior to the mesonephros, it becomes associated with the development of the metanephros, forming the nephrogenic tissue, which surrounds the blind end of the epithelial renal evagination, as was shown for the chick by Sedgewick. The above quotations were selected with a view of presenting the various views held concerning the histogenesis of the nephrogenic tissue.

We may now resume a consideration of the anlage and early developmental stages of the metanephros as observed in the rabbit. The renal evagination, which, as stated, buds dorsally into the nephrogenic tissue, in its further growth extends in a dorsal direction (the account here given follows Schreiner) pushing with it the nephrogenic tissue. This now assumes a dorso-median position with reference to the Wolffian duct, instead, as before, of lying in contact with it. In its growth, the renal evagination develops an enlarged blind end, which may be known as the primary renal pelvis and a stalk which may be designated as the ureter. The nephrogenic tissue, which surrounds the primary renal pelvis differentiates into an inner zone composed of epithelioid cells, which immediately surround it and an outer zone which presents the appearance of a condensed mesenchyme, which shows no distinct demarcation toward the surrounding mesenchyme; the two zones form the metanephrogenic tissue which has become separated from the mesonephrogenic tissue. As development proceeds, the primary renal pelvis grows in a dorsal and cephalad direction and elongates in an antero-posterior direction; at the same time, it begins to rotate on its axis in such a way as to make its dorsal surface have a more lateral position. The ureter likewise elongates and curves cephalad. The metanephrogenic tissue with its inner and outer zones is clearly recognized and surrounds the primary renal pelvis as a continuous layer. In slightly older embryos, the primary renal pelvis reaches a position dorsal to the posterior end of the mesonephros. In shape it has become still more elongated and presents two slightly enlarged ends with a narrower middle portion from which arises the ureter; it shows thickenings and buddings in its wall which in slightly older stages are clearly recognized as evaginations, the anlagen of the primary branches of the primary renal pelvis. The primary renal pelvis now consists of a narrower middle portion, from which arises the ureter and two enlarged ends and from it and more particularly from the narrowed middle portion, there spring three pairs of branches, each of which, as soon as clearly differentiated, presents a short stalk and a bulbous end. The entire metanephros now has a position which is dorsal to the hind end of the mesonephros. The metanephrogenic tissue, which, during the earlier stages, formed a continuous layer entirely surrounding the primary renal pelvis, presents a different disposition with the appearance of the primary branches and this applies more particularly to its inner zone, which, while it shows the structural appearances observed in earlier stages, presents a characteristic distribution. On the appearance of the primary branches, the inner zone of the metanephrogenic tissue no longer surrounds the entire primary renal pelvis, but only its enlarged extremities and the bulbous ends of its branches, the narrowed middle portion and the stalks of the branches being free from it. The inner zone of the metanephrogenic tissue is clearly recognized both by its staining reactions and by its structural characteristics. The primary renal pelvis and its branches, as also the inner zone of the metanephrogenic tissue, are surrounded by a tissue that stains less deeply than the inner zone and presents fewer nuclei, the outer zone of the metanephrogenic tissue. The entire renal anlage is surrounded by mesenchymal tissue, containing relatively few nuclei, these having a more or less concentric arrangement. For a fuller discussion of the anlage and early developmental stages of the renal evagination and the accompanying changes presented by the nephrogenic tissue as observed in the rabbit, the reader is referred to Schreiner’s paper (pages 98-121). My own observations confirm his results in full except as concerns the anlage of the metanephrogenic tissue, where the necessary stages are wanting in the material at my disposal. A separate discussion of the anlage and early developmental stages as observed in cat, pig, and human embryos does not seem necessary here, as this would involve unnecessary repetition, since the types studied present great similarity in the shape of the renal anlage and of the earlier stages of its metamorphosis. This is true, not only when considering types with simple non-lobulated kidneys as the cat and rabbit, but also when comparing these with types having lobulated kidneys as man and pig. In each type a renal evagination grows in a dorsal direction into the nephrogenic tissue and in its further growth differentiates into a primary renal pelvis and ureter, the former being enclosed and surrounded by the nephrogenic tissue, which in rabbit and human embryos permits of a differentiation into an inner and outer zone of nephrogenic tissue, as described by Schreiner, while in pig and cat embryos of corresponding stages, a differentiation of nephrogenic tissue into two zones is at this stage not made with certainty. (Compare Schreiner, pages 121 to 128 and pages 138 to 146.) The further development of the primary renal pelvis and nephrogenic tissue is for cat, pig, and human embryos much the same as above described for the rabbit. For each type, with the appearance of the primary renal branches of the primary renal pelvis, the inner and outer zones of the nephrogenic tissue may be clearly made out, the inner zone breaking up into cell groups which enclose and surround the ends of the branches as these become differentiated. At this stage, the primary renal pelvis for each type studied and modeled presents a middle portion of somewhat irregular shape, the primary renal pelvis proper, from which arises the ureter and an anterior and caudal end, slightly enlarged and more or less lobulated (depending on the stage of development) and three pairs of branches connected with the middle portion; these are not, however, made out with the same degree of clearness and do not present quite the same arrangement in the different types studied. These three pairs of branches are quite readily made out in cat embryos and present an arrangement not unlike that seen in the rabbit (text-figure 21 B, Schreiner), while in pig embryos the grouping of the primary branches is not so regular and only after they have attained some size is it possible to make out clearly what may be regarded as three pairs of branches. This, though to a less extent, is true also of human embryos. Attention may, however, here be called to the fact that models of the primary renal pelvis and its branches, in embryos of the same genus and of about the same age, even of the two kidneys of the same embryo (irrespective of size) present slight variation in the form of the primary renal pelvis and in the arrangement of the branches. A difference is also noted in the different types in the shape of the ureter as it enters the primary renal pelvis. In rabbit and cat embryos, this presents only a slight funnel-shaped expansion, while in pig and human embryos the expansion is much greater and is compressed in a dorso-ventral direction with its long axis parallel to that of the renal pelvis. The enlarged anterior and caudal ends of the primary renal pelvis, soon after the anlage of the three pairs of branches to which reference has been made, present, as development proceeds, more and more marked irregularity of form and develop each two, sometimes three, branches, which in appearance are like the other branches, showing a slightly narrowed stalk and enlarged ends; at the same time, the inner zone of the nephrogenic tissue which enclosed and surrounded the enlarged ends of the primary renal pelvis, breaks up into masses which surround only the bulbous ends of the resulting branches. In Fig. I, A and B, are reproduced two models, obtained by wax reconstruction, of the ureter, renal pelvis and branches of a cat and a human embryo for a stage slightly older than above discussed, in that the primary branches had already undergone secondary division. In these drawings, the nephrogenic tissue, for the sake of clearness, is not included. The models are purposely shown from different aspects, the one (A) giving a lateral view, the other (B) a dorsal view with reference to the position of these structures in the respective embryos. In both figures, in A more clearly than in B, the three pairs of primary branches are still discernible. The bulbous extremities of the primary renal pelvis described for earlier stages show here a division into branches, more clearly seen in B than in A, the former representing a slightly older stage.


Fig. 1. Wax reconstruction of the ureter, primary renal pelvis, and branches. X50. A, cat embryo (No. 2), 13 mm. in length;B, human embryo (No. 5), neck-breech, 16 mm., head-breech, 20 mm. In each figure only about one-third of the length of the ureter is represented.

The primary branches of the renal pelvis, or, as they may hereafter be known, the primary collecting tubules (Nierengangiste—Schreiner), extend to near the periphery of the renal anlage. Tach shows, as has been stated, a distal enlargement, which is known as the ampulla (primitive renal vesicle—Haycraft), and which is surrounded by a cap of tissue which we have described as the inner zone of the metanephrogenic tissue. Each ampulla, in its further development, enlarges, the distal wall of the enlargement becoming somewhat flattened and two lateral buds are developed; the primary collecting tubule now presents the appearance of a T or a Y when seen in longitudinal section or in a reconstruction. The distal end of each bud, soon after its beginning, develops a new ampulla. The inner zone of the metanephrogenic tissue which surrounds the primary ampulla as a continuous cell-mass, begins to show a separation into two parts as the ampulla becomes flattened and the separation becomes complete as the buds or lateral branches develop, each becoming in this way capped by an inner zone of metanephrogenic tissue. The stage here reached is the one shown in the reconstruction reproduced in Fig. 1.

Renal Vesicles

In Fig. 2 is shown a portion of a longitudinal section of a developing kidney of a human embryo 18 mm. in length and presenting essentially the same development of primary renal pelvis and branches as that in B of Fig. 1; this shows a longitudinal section of a primary collecting tubule, a, the distal end of which shows an ampulla, slightly flattened and presenting on each side a lateral extension recognized as the anlage of a branch. The section from which the sketch was made does not pass through the center of the tubule. It is owing to this that its wall has the appearance of being composed of stratified epithelium. In other sections of this tubule, as also in sections of primary collecting tubules at corresponding stages from cat, rabbit, and pig embryos, it may be seen that their wall is composed of a single layer of cylindrical cells, varying somewhat in length, the nuclei of which are not always in the same plane. In the tissue surrounding the tubule and ampulla& here figured, the following may be seen: Immediately surrounding the lateral extensions of the ampulla and extending for a short distance along the tubule there are recognized groups of cells, 6, 6’, which may be separated from the surrounding cells, These groups of cells we may know as the inner zone of the metanephrogenic tissue. The cells of this tissue are indistinctly bounded and possess relatively large oval nuclei which stain rather deeply and have a radial position with reference to the ampulla and tubule. In the preparation figured they are arranged in two rows quite clearly defined. This inner zone of the metanephrogenic tissue presents a sharp demarcation toward the ampulla and tubule, emphasized in the preparation sketched by reason of the fact that the ampulla and tubule were slightly contracted during the process of hardening. Herring has called attention to similar appearances presented by his preparations. In the relatively thin sections into which my entire material was cut, the distinct demarcation between the inner zone of the metanephrogenic tissue and the epithelium of the primary collecting tubules and their ampullar enlargements may nearly always be readily made out, if the plane of the section passes through the lumen of the tubules and their ampullar enlargements, thus giving a cross section to their epithelial walls.


Fig. 2. From a longitudinal section of a developing kidney of human embryo (No. 4), 18 mm. in length. xX 233. A, primary collecting tubule with ampulla; b, b’, inner zone of metanephrogenic tissue; c, outer zone of metanephrogenic tissue; d, anlage of capsule; e, renal vesicle.


Such appearances as described by Sedgewick, when he states “Some of the larger columnar cells of the kidney tubules become branched, the processes being continuous with the processes of the branched cells of the kidney blastema. In fact, every stage between a columnar lining cell of the tubule and a branched cell of the blastema is visible”—-I have not observed. The same may be said of the observations of Riede, who regards the epithelium of the renal evagination and of the primary collecting tubules as contributing to the formation of the renal blastema. t is only in relatively thick sections or in sections which pass obliquely through the epithelial walls of a primary collecting tubule without including the lumen, in which the nephrogenic tissue overlaps the tubular epithelium that a distinction between the two tissues is not readily made. Herring, who speaks of a cap or mantle of cells lying over the end of each ampulla, speaks of a sharp line of demarcation between the tube and the cap or mantle of cells. Ribhbert describes groups of cells which surround cap-like the ends of collecting tubules. These oups consist of two or three layers of epithelium-like cells which may be separated from collecting tubules on the one side and from “renal blastema” on the other. Schreiner, for all the types studied by him, describes and figures a distinct demarcation between the inner zone of the metanephrogenic tissue and the primary collecting tubules (Nierengangiste).


Immediately surrounding the inner zone of the metanephrogenic tissue there is a tissue in which the cell boundaries are also indistinct, with relatively large, round or oval nuclei, which show no definite arrangement, c, and which do not stain so deeply as the nuclei of the inner zone. This constitutes the outer zone of the metanephrogenic tissue. This zone blends with a tissue which is recognized as mesenchymal tissue. In the mesenchymal tissue, there is recognized a layer in which the majority of the nuclei show an elongated oval form and fairly regular arrangement, their long axis being parallel to the outer boundary of the kidney anlage, entirely surrounding it. In this layer is recognized the anlage of the capsule of the kidney, d. External to it, there is seen a mesenchyme containing relatively few nuclei, not sketched in the figure. The entire renal anlage measures in the embryo from which Fig. 2 was taken almost exactly 1 mm. in length. In the stained sections it is readily recognized with the naked eye as a small area, staining more deeply than the surrounding tissue and having a bean or kidney shape. The appearances presented in sections of the developing kidney of rabbit, cat, and pig embryos for corresponding stages are in all essentials as here described and figured for the human embryo. In each type the inner zone of the metanephrogenic tissue consists at this stage of generally two, sometimes three, layers of cells, which, as other observers have stated, have the appearance of epithelial cells, always surrounding the ampulle of the primary collecting tubules or of their branches much as shown in Fig. 2. The same may be said as concerns the structure and disposition of the outer zone of the metanephrogenic tissue and of the capsule anlage.


If the inner zone of the metanephrogenic tissue found surrounding the right ampullar extension as shown in Fig. 2 (0’) is traced in sections preceding and following the one shown in the figure, it will be seen that its border is not for its entire cireumference an even one, but that it presents a bud-like prolongation which extends for a short distance along the side of the collecting tubule. In this prolongation, which is here cut through its center, the cells show an arrangement in two distinct layers, continuous at the end of the prolongation. I was led to recognize this fact by Schreiner’s description of similar stages. Such bud-like prolongations of the inner zone of the metanephrogenic tissue early acquire a narrow lumen, around which the cells assume a radial position, certain cells of the bud in the region of its junction with the main mass of the nephrogenic tissue turning with their inner ends toward the lumen. In this way the bud becomes separated from the main mass of the inner zone. In the figure this process of separation is shown at its very beginning ; a lumen is made out with difficulty and one cell, the fourth in the inner row, appears to have been fixed in the act of turning. In the further differentiation of such a cell-mass, the lumen increases in size and the cells surrounding it increase in length, becoming more distinctly columnar in shape. The whole presents now the appearance of a small vesicle, the wall of which is formed by a single layer of columnar cells, which during its differentiation has completely separated from the nephrogenic tissue. Such a vesicle is shown to the left in Fig. 2 (e). A number of investigators have observed such vesicles and have interpreted them as representing anlagen of uriniferous tubules. They were first described and quite correctly figured by Emery, who speaks of them as “ vésicules rénales,” later by Riede, very briefly by Hamburger, Chievitz, and Ribbert, and quite accurately by Herring, whose excellent photographic reproductions are worthy of study, and finally by Schreiner, who gives a minute and accurate account of their origin and structure in the different types of animals studied by him. The account here given, based on sections of human embryos, is readily verified in sections of rabbit, cat, and pig embryos of corresponding stages. In each type small vesicles, which we shall designate as renal vesicles (following Emery, not to be confused with the primitive renal vesicles as described by Haycraft) are differentiated from the inner zone of the metanephrogenic tissue in the manner above described. The first renal vesicles differentiate in the types of embryos studied by me simultaneously with the anlage of the two branches into which the branches (primary collecting tubules) of the primary renal pelvis divide. That the renal vesicles have no connection with the primary collecting tubules may generally be made out by tracing these structures through a series of relatively thin sections; wax reconstructions of the primary collecting tubules and of the renal vesicles give, however, conclusive evidence of their independence.


Investigators who hold that the uriniferous tubules are developed by a process of budding from the primary, secondary and further branches of the epithelial renal evagination do not recognize the renal vesicles as here described. As they can not have escaped their notice entirely, it must be assumed that they are regarded by them as continuous with the developing colleeting tubules at all stages of their development and that they were thus interpreted as solid or hollow buds of the collecting tubules. Few of the contributions to which reference is here made contain satisfactory accounts of the earliest stages of the development of the uriniferous tubules nor are they accompanied by figures which clearly portray these stages. The figures presented are, in the great majority of instances, of stages where a direct continuity between collecting tubule and uriniferous tubule can not be questioned. Certain of the figures to which reference is here made showing earlier stages of kidney development deserve brief consideration. We may mention Fig. 581 of Kolliker’s Entwickelungsgeschichte des Menschen und Héheren Thiere (1879), which shows a longitudinal section of the kidney of an embryo rabbit 16 days old. In this figure are shown several primary collecting tubules (‘‘ Fndsnrossen des Ureters oder Ampullen’’), showing T or Y-shaped division of their distal ends and at least seven renal vesicles, if I may be allowed to interpret the figure in the light of observations made on my own sections of rabbit embryos of about corresponding age. In the accompanying text. Kélliker states that by further growth of the branches of the collecting tubules. these form the uriniferous tubules: no mention is made of the renal vesicles. In Figures 1, 2, 3, and 6 (of Plate XXIV) of Léwe’s article, sketches of the entire kidney, as seen in longitudinal section of rabbit embryos of 5, 10, 20, and 50 mm. length respectively are shown humerous renal vesicles in various stages of development in close relation with a tissue, which from its form and position must be regarded as the inner zone of the nephrogenic tissue. Liwe, who recognized the cel!-masses, has interpreted them as renal vesicles and traced their origin to Braun’s cords, stating that from them is developed the endothelium of the capillaries of the Malpighian bodies, while all parts of the uriniferous tubules with the epithelium of Bowman’s capsule are derived from the primary ureter branches. Again in Figs. 40 and 41 of Strahl’s communication (kidneys of human embryos of 28 mm. and 35 mm. length respectively. the inner and outer zones of the nephrogenic tissue and renal vesicles are recognized. Stoerk’s series of figures grouped under Fig. 2, giving in a ‘‘semi-schematic’’ way the development of the ends of the “ureter branehes”’ and the anlage of the Malpighian bodies (Nieren-kirperchen} show that he has not observed the renal vesicles, but, as No. 4 of this series of figures would indicate, he has interpreted the renal vesicles as buds of the ureter branches, as the position of the downward growing buds, as there figured, coincides with the relations shown by renal vesicles and primary ureter branches at a corresponding stage of development. Mention was made of Stoerk’s view of the anlage of the uriniferous tubules on page 5. Toldt, whose observations are frequently quoted as giving conclusive evidence of the development of the uriniferous tubules by a process of budding or further growth of the ureter branches, removed the kidneys from young embryos, stained them in hematoxylin or carmine. cleared them in turpentine and placed them on a slide as a whole. In such preparations, the primary branches of the ureter could he traced without interruption to the periphery of the organ where they terminated in enlargements. A further examination of the ureter branches designated by Toldt as “ Zellsprossen” with higher magnification showed that they grew forward first as solid buds which later attained a lumen. In Fig. 1 of the plate accompanying his article (kidney of cat embryo 13 mm. in length) is reproduced such a preparation. This shows however only ureter, primary renal pelvis and its primary branches, surrounded by kidney blastema and gives no evidence of the anlage of the uriniferous tubules. It should be remembered that it is conceded by the majority of observers that the epithelium of the nrimary renal pelvis and its branches is derived from the renal evagination by growth and budding. The figures given by Toldt and obtained from sections and teased preparations to show the anlage of the uriniferous tubules are of more advanced stages. It must, therefore. be stated that the method selected by Toldt to show the anlage of the uriniferous tubules is not a suitable one. The figures given by Pye, Nagel, Golgi. Minot, Haycraft, Von Ebner, and Disse show that they are dealing with developmental stages that do not represent the anlage or the beginning of the uriniferous tubules but more advanced stages where union between tubular anlage and collecting tubule had already taken place or that when earlier stages are represented as for instance by Disse (Fig. 77), it seems apparent that a continuity of the discontinuous structures is simulated by an overlapping of the two structures. In sections passing through the epithelium of an ampullar enlargement, without passing through its lumen and through the inner zone of the nephrogenic tissue and a renal vesicle, it often seems as if these structures were continuous, presenting the appearance of a bud growing from the ampullar enlargement of the primary collecting tubule. This is also true if the section passes obliquely through these structures. In such sections, especially if relatively thick, the inner zone of the nephrogenic tissue, which, as has been stated, resembles epithelial tissue, appears as a continuation of the epithelium of the ‘collecting tubule. Haycraft makes the statement that the most conclusive evidence in favor of the view that the epithelium of the kidney tubules arises from the blastema “ would be the presence of isolated masses of cells and their subsequent junction with the tubules, but of this, as we have seen, there is no proof.’ ‘‘ What we have is an appearance at the tips of the collecting tubules which suggests to the minds of many observers that the cells of the blastema gradually transform themselves into epithelium.’ He further states that such appearances are due to “ nothing more nor less than oblique sections of tubules, not through their extremities, but through bends in their course.” To this it may be answered that reconstructions show conclusively the presence of isolated cell-masses—renal vesicles, the anlagen of uriniferous tubules—which subsequently join the collecting tubules and further that the very argument which Haycraft uses to point out the sources of error of those who hold to the discontinuous origin of the uriniferous tubules from special cell masses may be used with equal pertinence to explain the sources of error of observers who hold that the uriniferous tubules are developed by a process of budding from the collecting tubules, namely that the latter have been led to interpret as continuous structures certain discontinuous structures—primary collecting tubules, tnner zone cf metanephrogenic tissue and renal vesicles—which by reason of their close relation and a certain resemblance in structure of their constituent cells appear in oblique sections as forming a continuous whole. My own observations, pertaining to human, cat, rabbit and pig embryos, as may be apparent from statements here made, have enabled me to confirm the observations of investigators who recognize a discontinuous origin for the uriniferous tubules and who have described small vesicles, variously known as Blaschen, acini, or renal vesicles, as the anlagen of the uriniferous tubules proper.


Development of the Collecting Tubules and their Relation to the Renal Vesicles

The further growth of the kidney is accomplished by a further division of the branches of the primary renal peJvis and their differentiation into the straight collecting tubules, by a constant new formation of renal vesicles and by a differentiation of the renal vesicle into the uriniferous tubules and their union with the collecting tubules. Each primary collecting tubule early divides, as has been stated, into two branches, each of which shows a distal enlargement, an ampulla, capped with a layer of nephrogenic tissue. Each of these branches divides again into two branches, the division beginning with the ampullar enlargement. With the formation of this second series of branches, the zone of nephrogenic tissue which surrounded the ampulla of each primary branch separates into two parts, each of which surrounds the end of one of the resulting branches. Several similar divisions follow in relatively quick succession and with the division of each end branch the nephrogenic tissue which surrounds it separates into parts, which in each instance surround the ends of the resulting branches. The end branches from each division develop ampullar enlargements, which are found at the periphery of the organs under the developing capsule, which enlarges as the kidney develops. (In the developing kidney of human embryos, the end branches are seen to end under the capsule and at the boundaries of the primary lobules, as will be stated more fully later.) The repeated division of the branches of the primary renal pelvis, as here briefly sketched, results in systems of branched, relatively straight tubules, which extend from the pelvis of the developing kidney to the periphery of the organ and are recognized by authors generally as the anlagen of the straight collecting tubules. Such tubules are lined throughout by epithelium having relatively clear protoplasm and round or oval nuclei, the arrangement of which differs somewhat in the earlier branches from that found in the later branches. In the former, the larger tubules, those nearer the pelvis, the epithelium is for the greater part of embryonic life of a pseudostratified type, while in the smaller tubules, those nearer the periphery, the epithelium is simple columnar. The division of the end branches of these tubular systems continues without much variation from the manner here described to about the time of birth or until the final number of collecting tubules has been formed. Hamburger states that the division of the collecting tubules terminates in the human embryo in the fifth month of fcetal life, in the pig in embryos about 14 cm. in length, in the rat and mouse at about birth. The details of the development of the collecting tubules will not be entered upon here, as the necessary data are not yet in my possession. This requires a much more extensive series of reconstructions at different stages of development than I have been able to make, and not for one animal, but for a series of animals, as my limited observations indicate that, while the general plan of development of the straight collecting tubules is the same for different mammals, variations in detail are to be looked for. This may be seen also from Hamburger’s account, who briefly considers this question, basing his observations on teased preparations. For the purpose of this account, which is concerned with the development and shape of the uriniferous tubules proper, the brief statement will suffice that the straight collecting tubules are developed by a process of continuous growth and of repeated divisions of the ends of the tubules which grow from the primary renal pelvis. These divisions take place at the periphery of the organ (or of the primary lobes, when present) immediately under the capsule. It has been stated that with each division of the ampullar enlargement of an end branch of a system of developing collecting tubules, the inner zone of the metanephrogenic tissue likewise separates into parts which surround the ends of the resulting branches. During the development of the kidney, this tissue proliferates by mitotic division. At all stages of development it is found surrounding the ampullar enlargements of the end branches of the developing collecting tubules as a layer consisting of one or two rows of cells, possessing oval nuclei which stain relatively deeply, the layer being in contact with epithelial cells which form the wall of the ampullar enlargement. This nephrogenic tissue is therefore found at the periphery of the developing kidney immediately under the capsule. From this tissue, with each successive division of the ampullar enlargements of the end branches of the collecting tubules, new generations of renal vesicles are differentiated in @ manner similar to that previously described for the first generation of renal vesicles. While new renal vesicles are thus differentiating about the ends of the terminal branches of the collecting tubules, those previously formed are developing into uriniferous tubules. Those first formed show the greatest degree of development, the various generations of renal vesicles undergoing essentially the same metamorphosis in developing into uriniferous tubules. Beginning with a relatively early stage in the development of the kidney through the entire period when new tubules are forming, there may therefore be observed a peripheral zone containing the end branches of the collecting tubules showing ampullar enlargements surrounded by nephrogenic tissue, forming and formed renal vesicles, and of these others which show the earlier stages of development leading to the formation of uriniferous tubules. This subcapsular zone stains somewhat more deeply than other portions of the developing kidney and may therefore be recognized with the naked eye. It surrounds the entire kidney except the place where the ureter enters. It has repeatedly been recognized as the zone where the earliest stages of the developing uriniferous tubules are to be found and is described by Hamburger and Stoerk as the neogenic zone (“die neogene Zone ”— Hamburger). In this way new generations of uriniferous tubules develop outside of those previously formed, the latter thus coming to lie deeper down in the parenchyma of the kidney and showing according to their age more or less advanced stages of development. The period when the new formation of renal vesicles ceases varies somewhat for different animals. In the rabbit, I have observed their formation as late as the first week after birth, although the number of newly forming renal vesicles is for the later period of embryonic life relatively small. In the cat, newly forming renal vesicles were observed in a kidney removed from an embryo a short time before birth. Herring states that no more tubules are formed in the human kidney after the 8th month of feetal life. Stoerk, who has considered this question quite fully, agrees with Herring. Toldt, on the other hand, states that new Malpighian corpuscles form in dog and man in the entire peripheral part of the kidney for 8 to 10 days after birth. My own human material is too limited to be of any value in determining this question.

Differentiation of the Renal Vesicles

We may now consider the further development of the renal vesicles. As has been stated, these are differentiated from the inner zone of the metanephrogenic tissue and, when completely separated, consist of a single layer of columnar cells with oval nuclei which stain relatively deeply and surround a central lumen. At this stage of their development they are generally quite definitely circumscribed and have a shape which varies from that of an irregularly spherical body to that of an egg. They le in close relation with the collecting tubules and their ampullar enlargements, these being often slightly flattened in the region of their contact with the vesicles. At least two renal vesicles develop in connection with each ampullar enlargement; these do not, however, present the same degree of differentiation and development, as may be seen from Fig. 2, and is more clearly seen in renal vesicles which develop in connection with the ampullar enlargements of the end branches of collecting tubules which appear after the first and second division of the branches, which arise from the renal pelvis. The branches resulting from each successive division of a collecting tubule form with this soon after their anlage a T-shaped structure; in their peripheral growth, the angle between such branches becomes smaller and they form with the collecting tubule a Y-shaped structure, each branch developing an ampullar enlargement surrounded by nephrogenic tissue. A renal vesicle develops from the nephrogenic tissue on the outside of each branch (therefore nearer the pelvis of the kidney) earlier than from the nephrogenic tissue between the branches. (See also Schreiner, especially textfigure 34.) The renal vesicles, soon after their separation from the nephrogenic tissue, increase in size by active proliferation of their cells by mitotic cell division, the vesicle elongating somewhat and coming in close contact with the ampullar enlargement of the collecting tubules. At the same time it may be observed that the outer wall of the vesicle, that away from the collecting tubule, and especially its upper portion, becomes thicker than the wall of the vesicle in contact with the collecting tubule. This thickening of the outer wall of the vesicle was first described by Schreiner and fully discussed by him. He states, and in this my own observations confirm his account, that the cells of the middle and upper portions of the outer wall of the vesicles elongate, the cells here appearing longer when the vesicles are in sagittal section (*) than in other parts of the vesicles and that evidences of cell division are often seen.

  • 1 By a sagittal section of a renal vesicle is here meant a section which cuts a collecting tubule in longitudinal direction and parallel with its lumen and passes at the same time through a renal vesicle which may develop by its side, thus cutting the renal vesicle in a plane which passes through the middle or nearly the middle of its outer wall. The renal vesicles seen in Fig. 2 and A of Fig. 3 are cut in sagittal section. The plane of a frontal section of a renal vesicle passes perpendicularly through it and would intersect the plane of a sagittal section at right angles.


In such a section it will be seen that the lower inner ends of these elongated cells, which no longer hold a radial position to the lumen of the vesicle, but are inclined to its long axis, slightly overlap the inner ends of the cells which form the lower portion of the outer wall of the vesicle, so that a portion of the outer wall of the vesicle presents the appearance of a two-layered epithelium. As development proceeds, the outer wall of the vesicle further thickens and encroaches on its lumen, which in sagittal sections now presents the appearance of a hook-shaped space. At about this time there appears on the outer wall of the vesicle over its thickest portion a slight depression, beneath which a cleft makes its appearance; this begins to separate the thickest portion of the wall of the vesicle into two layers. This cleft deepens as the two layers of cells become more distinctly separated. In A of Fig. 3 is shown a sagittal section of a renal vesicle at this stage of development. The section sketched does not pass exactly through the center of the vesicle, nor is it quite parallel to its long axis. This needs to be remembered in examining this figure, as the arrangement and size of the cells forming the different parts of the wall of the vesicle are not quite what might be expected from the foregoing description. The reproduction gives the most typic section of the series of sagittal sections of the vesicle from which the reconstruction was made which is shown in A of Fig. 4. In A of Fig. 3 is shown an ampullar enlargement of a terminal branch of a collecting tubule surrounded by nephrogenic tissue, a rena] vesicle and the surrounding mesenchyme and a portion of the capsule. In the wall of the vesicle away from the collecting tubule may be observed a slight depression and beneath this a cleft. The nuclei of the cells adjacent to the cleft are stained a little more deeply than the other nuclei of the vesicle. Such an appearance is now and then seen, though not characteristic of this stage. In the reconstruction, this cleft appears on the surface as a narrow depression placed nearly transversely to the long axis of the vesicle, a little above its center, though not extending across its entire wall, and is therefore scarcely seen in the exposure of the model as sketched. That portion of the vesicle, which in sagittal section shows the narrow cleft, is in reality a small pocket, the upper and lower walls of which are nearly in contact at this stage of the development. Similar appearances I have observed in a number of other wax reconstructions of this stage. This pocket is not developed primarily by an infolding or invagination of the outer wall of the vesicle, but differentiates in a thickening of its outer wall. This thickening results from a slight readjustment of the cells constituting this part of the vesicle as well as by their proliferation. In the further development, this cleft enlarges by deepening and by extending laterally so as to involve more than the outer wall of the vesicle. In this way the lower and outer part of the original vesicle becomes separated from the main part of the vesicle and presents the appearance of a lip, which projects upward toward the periphery of the kidney. Into this lip-shaped portion the lumen of the vesicle extends. While these changes in form and structure which affect primarily the lower part of the vesicle are taking place, the upper part of the vesicle elongates, sometimes more and sometimes less, growing toward the respective collecting tubule, more correctly its ampulla; at the same time, a slight depression appears in the uppermost part of the inner wall of the vesicle, that in apposition with the wall of the collecting tubule, which emphasizes the curvature of the upper part of the vesicle toward the collecting tubule. In A of Fig. 3 is shown the first indication of this second depression in the wall of the renal vesicle at a point marked by a cross. The end result of these changes in form and structure on the part of the renal vesicle are represented in B of Figs. 3 and 4. It may be seen that by a deepening of these clefts, the more prominent one in the outer wall, the less prominent one in the upper portion of the inner wall of the original vesicle, and by a growing of its upper end toward the collecting tubule, the vesicle has been altered in its shape so as to present in sagittal sections and at times also in reconstructions the form of an 8S. In the sagittal section of this renal vesicle, or, as we shall now know it, the tubular anlage (the word uriniferous being understood) is cut longitudinally and through its middle in the section sketched for nearly its entire length, the upper portion of the anlage deviating a very little from this plane of section. The reconstruction of this tubular anlage, B of Fig. 4, does not show this S-shape as clearly as certain of the sections of it. The upper bend of a tubular anlage of about this stage presents a circular and very narrow lumen. In the tubular anlage figured, the lumen of its upper bend appears clearly only in the section sketched. In frontal sections of tubular anlagen of this stage, in which this upper bend would appear in cross or slightly oblique section, the existence of a small lumen in this portion of the anlage may be clearly made out, the part itself being round or nearly so. It constitutes, therefore, a tubular structure, its wall being made up of a single layer of columnar cells with oval nuclei. Frontal sections of a tubular anlage of this stage further show that its lower bend does not represent a structure having a tubular form, but is flattened from above downward, presenting in such sections the appearance of a crescent with concavity directed upwards toward the periphery of the kidney. Reconstructions of tubular anlagen of this stage show that this portion presents the shape of the bow! of a spoon or of a saucer with the concavity turned toward the other parts of the anlage. In making this comparison, it is to be understood that this structure is not solid, but double-walled, the enclosed space, which is continuous with the lumen of the other parts of the anlage, having a similar shape. At this stage in the development, the upper concave wall of the structure is composed of columnar cells, while the lower or convex wall is composed of cubical cells. Both in the series of sections of the tubular anlage shown in B of Fig. 3, and also in the reconstruction of the same, B, Fig. 4, it may be clearly seen that it is not continuous with the ampullar enlargement of the collecting tubule. It is in close contact with it but not continuous with it. In C of Figs. 3 and 4 is shown a tubular anlage which is only slightly further advanced in its development than the one shown in B of the same figures. The section sketched shows, however, a continuity of the lumen of the tubular anlage and that of the ampulla of the collecting tubule, although, as is evident from the sketch, the place of union of the two previously discontinuous parts may yet be made out, partly by reason of the position of the nuclei of the respective cells, also because there is as yet a slight constriction at the place of fusion, this being not as yet complete. The modus operandi of this union between tubular anlagen and collecting tubules has been discussed by Schreiner, who states that he has observed in the tubular anlagen or in the ampullar enlargement of the collecting tubule at a stage which he has recognized as just previous to a stage in which there is union of the two, a cell in mitotic division or cells which by their structure and staining show that they have just completed division. This division of cells at the place of contact of the upper end of the tubular anlage and the ampulla of the collecting tubule, Schreiner associates with the fusion of these parts and with the formation of a continuous lumen. This stage is rather difficult to find, as it is not readily recognized unless the respective tubular anlage is seen in a favorable sagittal section. In the tubular anlage, a section of which is here shown, there is no evidence which would indicate that one or more of the cells situated at the place of its junction with the collecting tubule had just completed its division. In my own preparations I have not found cell division at the place of contact between tubular anlagen and collecting tubules more frequent than in other parts of these structures in a stage which might be interpreted as just prior to a fusion of these structures. My own observations would, therefore, confirm only in part those of Schreiner as concerns this point. I have, however, accepted Schreiner’s account of the processes of union of the tubular anlagen and collecting tubules as the most satisfactory that can be given. In Fig. 5 are reproduced a series of wax reconstructions of the anlage and early developmental stages of uriniferous tubules obtained from rabbit embryos; in Fig. 6, a similar series obtained from cat embryos, and in Figs. 9 and 10, a primary collecting tubule, with its branches, the renal vesicles, tubular anlagen, and uriniferous tubules in early stages of development associated with them. These were obtained from kidneys of human embryos of 3 cm. and 6.5 em. length respectively. In A and B of Fig. 5 are represented in each instance a collecting tubule with prominent ampullar enlargement and a renal vesicle. In A the renal vesicle is of spherical shape, in B of egg shape, the latter representing a slightly older stage, showing, however, as yet no characteristic differentiation; both are distinctly separated from the respective collecting tubule. In € of Fig. 5 is reproduced a tubular anlage, which had united with the collecting tubule at a relatively early stage, before presenting the S-shape to which attention has been called. The lumen of this tubular anlage, as seen in sections of it, shows this shape more clearly than does the reconstruction. The same may be said of the tubular anlage shown in A of Fig. 6, the earlier stages of the series being here not reproduced. These two figures have been introduced to show that the tubular anlagen do not always present the same degree of development and differentiation at the time of their union with the collecting tubules. Characteristic and constant differences in this respect I have not observed for the different animals studied.


Fig. 8. A series of figures, A to J of sagittal sections of tubular anlagen and uriniferous tubules in early stages of development, showing successive stages in the development of the uriniferous tubules, from a human embryo of the seventh month (No. 16). x 160. Im each figure of this series, there is reproduced the most typical section of the several series of sagittal sections used in making the reconstructions shown in Fig. 4. (The corresponding tubules in Figs. 3 and 4, are designated by the same letter.)


Fig. 4. A series of models A to J, showing successive stages in development of tubular anlagen and early stages in the development of uriniferous tubules, with a portion of the collecting tubule to which each is attached; from a human embryo of the seventh month (No. 16). X 160.


Variations in the time of fusion of the tubular anlagen and the collecting tubules within the limits shown in these figures may be observed in a series of sections from developing kidneys obtained from embryos of the same species of animals. Such fusion does not take place, so far as my observations go, prior to a time when the renal vesicles show a distinct indentation of their outer wall, the lumen thus presenting the shape of a hook, but may take place before the inner upper portion of the vesicles or tubular anlagen show an indentation leading to the formation of the upper curvature; in this case the curvature develops after fusion has taken place. A study of the tubular anlagen shown in Fig. 9 and a comparison of these with those shown in Figs. 4, 5, and 6, will prove instructive, especially the two tubular anlagen seen to the left of the upper ends of the two prominent diverging branches of the collecting tubule. Since the latter are sketched from a different view than those of the previous figures, they represent tubular anlagen just after fusion with the collecting tubules and show clearly the saucer-shaped expansion of the lower bend of the S-shaped structure characteristic of this stage.

S-Shaped Stage in the Development of the Uriniferous Tubules

To characterize the S-stage of the development of the uriniferous tubules more clearly, one may speak for convenience of description of an upper S-curve, with concavity toward the collecting tubule; an S-middle piece or middle S-segment, and a lower S-curve with convexity toward the collecting tubule. In considering the tubular anlage as a whole, one may speak of its inner face or side, that turned toward the collecting tubule, and an outer side, that turned away from the collecting tubule and further of a front and back side or face, these with reference to a plane passing through the middle of a tubular anlage as in a sagittal section of the same, and finally of an upper and lower portion of the anlage, with reference to its attachment to the collecting tubule, which would mark its upper portion. In the same way we may speak of a portion of a tubular anlage as curving or growing inwards or outwards, upwards or downwards, and forward or backward. In the further description I shall make use of these terms without further comment. In this connection it needs to be recalled that renal vesicles and tubular anlagen develop in connection with each of the two end branches resulting from the successive divisions which occur in the course of the development of a collecting tubule. Favorable sections now and again show a collecting tubule with two more or less clearly differentiated end branches connected with two tubular anlagen seen in sagittal section. The whole structure presents the appearance of a Y or of an anchor with the arms bent toward the stem of the Y or shaft of the anchor (see Figs. 10 and 12). Assuming that the two tubular anlagen are in the S-stage, only the left one would in reality have the shape of a Roman §, while the right one would show a mirror picture of the same. This fact enables one readily to state whether any particular tubular anlage is placed to the right or left of a given collecting tubule. By right or left is meant the relations shown by these structures to the collecting tubule to which they are attached in any given section. In the series of figures showing reconstructions of tubular anlagen and early developmental stages of uriniferous tubules, as given in Figs. 3, 4, 5, and 6, I have for each stage of development selected a tubular anlage placed to the right of a collecting tubule. It seemed to me that this would assist materially in tracing the successive stages and would facilitate a comparison of similar stages. Tubular anlagen placed to the left of the collecting tubules show the same developmental stages which would appear in mirror pictures to those here given and show the same relations to the collecting tubules. They show similar inner and outer, front and back surfaces as above described, these designations having reference to the relations of any tubular anlage to the collecting tubule to which it is attached, independent of the fact that such anlage may be placed to the right or left of the collecting tubule. With this definition of the terminology to be used, we may now proceed to a fuller consideration of the S-shaped stage and state that the upper S-curve represents a tubule with narrow lumen having an outward curvature and extends without definite boundary into the S-middle piece, which is also of cylindrical shape, representing a short tubular segment also with narrow lumen and, like the upper S-curve, is composed of a single layer of cells with oval nuclei. When first recognized, it has a nearly horizontal position; but as development proceeds and the S-shape of the tubular anlage becomes more pronounced, it loses this horizontal position and inclines upward toward the collecting tubule. This portion of the anlage is not so clearly defined as the other parts and the relative time of its differentiation varies somewhat, as will be more fully stated later. The lower S-curve, as has been stated, is not of cylindrical shape, but from the time of its anlage is flattened from above downward and presents the form of a double-walled saucer or shallow bowl with concavity directed upward, the cavity which extends into this portion being likewise flattened and presenting a similar shape. The cells forming the upper wall of this structure are of columnar shape, those forming the lower wall of cubical shape or even more flattened, depending on the stage of development. The saucer-shaped structure becomes narrowed as the region where it joins the S-middle piece is approached and here gradually changes (in the most typical anlagen) from a flattened to a nearly cylindrical structure. The place of junction of the two parts is indicated by a sharp bend in the lumen of the tubular anlage as this is seen in sagittal sections and may be indicated by a nearly equally sharp bend when the anlage is seen in reconstructions. The lower end of the upper S-curve, with a portion of the S-middle piece, rests in the concavity of the saucershaped portion representing the lower S-curve so that only a narrow space separates these parts. In sagittal sections this space appears as a curved cleft and contains, soon after its anlage, a delicate strand of mesenchymal tissue. (See C of Fig. 3.) In D of Figs. 3 and 4 is shown a slightly older tubular anlage, which differs from the former in that the place of union between the tubular anlage and the collecting tubule is no longer recognized and in the more pronounced curvature of the anlage as a whole. This is especially clearly seen in the section of this tubular anlage shown in D of Fig. 3. In the reconstruction it will be seen that what appears in section as the lower S-curve represents in reality a shallow bowl, the edges of the saucer-shaped structure recognized in the former stage and figure having grown upward, thus deepening the concavity; also the space which separates this part of the anlage from the lower end of the upper S-curve and S-middle piece has increased somewhat and is now occupied by a vascularized mesenchyme, the section reproduced showing two capillaries, the one cut cross-wise, the other seen in longitudinal section. The mesenchyme contained within thé concavity of the lower S-curve has long been recognized as the anlage of a glomerulus, this portion of the tubular anlage, as may be stated now, forming Bowman’s capsule. My own observations lead me to think that the first capillary loop found within the mesenchyme occupying the concavity of the lower S-curve of a tubular anlage grows into this from without, as I have generally been able to trace a connection between it and the capillaries outside of the cleft occupied by the mesenchyme. To give definite answer to this question, however, it would be necessary to confirm the above statement on injected preparations, but the fresh material of the proper stage of development, obtained during the course of this investigation, was too limited to attempt this. This question has received only incidental mention by other investigators; of the more recent of these we may mention Schreiner, who simply states that “into the cleft there grow from without connective tissue and vessels,” and Stoerk, who, in speaking of the development of the S-shaped stage of the tubular anlage, states that “there is formed between the upper curve and the middle piece on the one side and the concavity of the lower curve on the other side a downward curving cleft, which takes up vascularized interstitial tissue, from which later the glomerulus is developed.” Herring, on the other hand, states that when the S-shaped tubule is formed, the space between the lower and the middle limb is occupied by some connective tissue cells; they are few in number and resemble the other cells which ard found in the matrix of the cortex. He further states that “From these cells I believe the capillaries of the glomerulus are formed in situ and not as an ingrowth.”


Fig. 5. A series of models A to F, showing successive stages in the development of uriniferous tubules in rabbit embryos.- x 160. A, #, and F, from rabbit embryo (No. 2) of 14 mm. length; B, C, and D from rabbit embryo (No. 3) of 18 mm. length. A and B show each a renal vesicle and a part of a collecting tubule with prominent ampulla; C and D early and late S-shaped tubule.


Fig. 6. A series of models, A to H, showing successive stages in the development of uriniferous tubules in a cat embryo 22 mm. in length. x 160.


The S-shaped stage in the development of the uriniferous tubule, especially characteristic when seen in sagittal sections, has long been recognized and was first correctly described by Toldt and is clearly brought out in Golgi’s semidiagrammatic figures of developing uriniferous tubules of mammals. The series of developmental stages leadin to the formation of the S-shaped tubular anlage have, I believe, been correctly described only by Schreiner, whose account my own observations, as given here, in the main confirmed.

Ribbert gives in a series of semidiagrammatic figures (Fig. 3 of his article) his view of the development of the S-shaped stage of the tubular anlagen. By means of these figures, he aims to show that the lower portion of the cell-mass from which a tubule is developed, in its growth turns sharply upward, toward the eriphery of the kidney. In this way, a cleft is formed between the elongation an e cell-mass from which it develops; the latter now makes union with the collecting tubule, the whole structure acquiring a lumen and the S-shaped stage of the tubular anlage is reached. Herring states that ‘By active proliferation of cells, the vesicle grows in length, but not as a straight tube; it becomes comma-shaped, the bend of the comma being always away from the collecting tubule with which it eventually joins.” ‘“ The comma is now in close contact with the ampulla, but the lumens are not continuous. As the comma-shaped body grows, it elongates, but the tail remains in the same position; further growth is upward toward the capsule along the end of the collecting tube. It grows more quickly than the latter and takes on another curve at its upper end, this time toward the ampulla. The result is an S-shaped body, with central! Iumen. When the S is well developed, its lumen becomes continuous with the lumen of the collecting tube.” In both of these accounts, the anlage of the lower curve of the future S-shaped structure, as above given, is missed. Hamburger states that when the anlage of the coiled uriniferous tubule has reached a diameter of 40 » to 50 », a small cavity develops in its center (renal vesicle) and shortly after this, a union between it and the ampulla is established and a short solid cord of cells, which extends from the peripheral end of the ampulla to the lateral wall of the vesicle develops. In its further development, the tubular anlage obtains a depression, always seen on the side of the anlage which is turned away from the ampulla with which it is connected; {ts wall sinks in somewhat, thus giving the cavity the form of a ‘“ half-moon shaped cleft;’’ this depression deepens and develops into a cleft and there is formed a ‘“wing-like process,” which lies against the side of the anlage and terminates with a sharp free border, which projects toward the surface of the kidney. When the anlage of the coiled uriniferous tubule has attained the size of 50 » to 60 » it still has a spheric shape’? but consists of 1, a bowl (Schale), the concavity of which is turned toward the surface of the kidney, 2, a short thick tubule of S-form, which unites this bowl with the ampuila.” This stage of the development corresponds with the S-shaped stage of other authors. Such early fusion of the anlagen of uriniferous tubules with collecting tubules as described by Hamburger I have not observed. This error of observation on his part (for such I take it to be) is, I believe, accounted for by the thickness of the sections which he examined (15 to 20 »). In sections of this thickness, it is often exceedingly difficult to state whether or not renal vesicles or tubular anlagen are merely in contact with the collecting tubules or continuous with them, unless the parts are most favorably sectioned, a Point to which I have previously called attention. That the depression on the outer side of the renal vesicle and especially the cleft which opens into it is not primarily formed by an infolding of the wall was brought out in describing its formation; the solid cord of cells uniting the ampulla with the renal vesicle, as described by Hamburger I have not observed. The upper portion of the renal vesicle retains a lumen as it elongates toward the collecting tubule and this becomes continuous with that of the collecting tubule at the time when fusion between these structures takes place.

Authors who regard the uriniferous tubules as developed directly from the collecting tubules are quite unanimous in their accounts of the formation of this S-shaped stage of the uriniferous tubules, stating that the end branches of the uriniferous tubules, or buds from these, grow for a short distance toward the pelvis of the kidney and then again toward the periphery, the lobule or bud thus becoming flexed, presenting first a concavity, then a convexity toward the collecting tubule. I have previously quoted Haycraft, Gerhardt, and Stoerk as concerns this point. Minot considered the capsule as playing an important réle in the formation of the tubular anlagen. He states: “The capsule seems to prevent the further elongation of the branch in its line of growth, and to force the end of the branch to curl over, thus by simple mechanical condition causing the formation of the anlage of the Malpighian corpuscle.” Gerhardt also states that the capsule offers a mechanical obstacle to the further growth of the straight tubules and thus gives the first impulse to the coil formation. Assuming for the moment that the uriniferous tubules are developed by a growth and budding of the collecting tubules, it must be evident that other factors than the one found in the resistance offered by the capsule to the further elongation of the branches of the collecting tubules, play a part in causing these branches to curl over and form the anlage for the uriniferous tubules, as in the developing kidneys of human embryos of from 3 em. to 6 cm. in length the neogenic zone is found, not only at the periphery of the organ, immediately under the capsule, but forms septa which extend nearly to the pelvis of the kidney and are found at the line of union of 4 to 6 primary lobules into which the parenchyma of the organ may at this early stage of its development be separated. These septa, which Haugh has termed “the primary columns Bertini,” are in reality composed of the neogenic zones, separated at the time when they are first recognizable and for some little time after by only minimal traces of mesenchymal tissue, which occurs here and there in small areas and does not present at this stage of development the relatively dense structure of the capsule, which dips down at the superficial boundaries of these primary lobules for a variable though always short distance. Uriniferous tubules develop on each side of these septa in the same way as under the capsule and it is evident from a study of sections that the end branches which reach these septa or primary columne Bertini do not meet resistance in their further growth by the capsule or by a tissue of like density, since such tissue is not found in the primary columne Bertini, when first formed and for some little time after.

In Fig. 7 is reproduced a portion of a section from a series of longitudinal sections of a kidney obtained from a human embryo measuring 6.5 em. in length (No. 11), showing the junction of two primary lobules. In this figure is represented a primary columna Bertini, which extends from the capsule nearly to the pelvis of the kidney and the renal parenchyma developing on either side of it. As will be observed, collecting tubules grow toward the septum from either side and renal vesicles and tubular anlagen develop on either side of it in a manner similar to those which develop under the capsule. For the greater part of its extent this columna or septum contains at the stage of development shown in the figure very little mesenchymal tissue. This is well developed only near the pelvis of the kidney, from which it extends outward for a short distance and here clearly separates the two lobules. For a fuller consideration of the primary lobulation of the developing kidney and of the primary columne Bertini, the reader is referred to Haugh’s paper, who considers these questions at some length.

Stoerk, in his setond paper, discusses and figures (Figs. 3-8) wax reconstructions of tubular anlagen showing the S-shape. I desire to consider somewhat more fully his observations relating to this stage of the development of the uriniferous tubules, as these observations are not in harmony in all particulars with my own. Stoerk in this paper begins his description of the development of the uriniferous tubules with a stage, which, in profile view, presents the appearance of an inverted question mark. This twisted structure simulates, as he states, in sections the appearance of an S-shaped tubule and is s> recognized by authors. With reservation, he adopts the same designation. In this he recognizes, for convenience of description, ® parts (and in this I have followed him), an upper S-curve, an S-middle piece and a lower S-curve. The upper S-curve passes without definite boundary into the S-middle piece. The lower S-curve grows upward toward the lateral bend of the upper S-curve; in this way, there is formed between it and the S-middle piece on the one hand and the concavity of the lower S-curve on the other hand, a curved cleft, into which vascularized mesenchyme grows and forms the anlage of the glomerulus. From his reconstructions, he was able to see that the lower S-curve is in reality not a tubule, but is spread


Fig. 7. A portion of a longitudinal section of the kidney of a human embryo measuring 6.5 cm. in length (No. 11), showing a primary columna Bertini, which extends from the capsule to near the pelvis of the kidney. X 80. Pcb, primary columna Bertini; c, capsule; pe, epithelium of pelvis; d, end branches of collecting tubules.

out, beginning with the place where the S-middle piece passes into it “into a thin, spherically curved and downward bellying structure with a sharp border, having the form of a triangle with rounded angles; the base of this triangle represents the upcurved, blind ending of the S-shaped tubule, as seen in sections. Over the middle of this structure with upward facing concavity is found just a little above it the junction of the upper S-curve with the S-middle piece.” he lower curve of the §, which is not solid but hollow has therefore the shape of an oyster shell (‘ Muschelschale’’) and, to continue the comparison, we may say with one having a deeper concavity with edges rolled in somewhat, the more fully developed the structure is.

The account of the further development of the lower S-curve as given by Stoerk I shall give in his own words, as it is particularly with this portion that I desire to take exception. He states (page 297): ‘‘ Die Muschel nimmt einerseits im Sinne der Fliche an Grésse zu, andererseits gewinnt sie an Wolbung, sodass sie zunichst der Form einer ein wenig verzerrten halben Kugelschale zustrebt (s. Fig. 3, 4 und 5); diese umwélbt die Uebergangstelle vom Mittelstiick in die obere S-Halfte und wird von dieser Kanilchenpartie fast bis zum Kontakt erfiillt; allmihlich wird dann auch das S-Mittelstiick zur Kugelschalenbildung herangezogen und geht in diese auf (Modell B), so dass nunmehr der obere S-Bogen tibrig bleibt, der, aus der Kugeischale aufsteigende, von deren Innenseite durch eben jenen schmalen von Zwischengewebe erfiillten Raum etrennt wird, der sich, wile erwihnt, im Schnittbilde als abwirts gekriimmter enger palt prisentiert.”

This double-walled structure, developing from the lower S-curve and the S-middle piece, with the enclosed mesenchyme, develops into Bowman’s capsule and glomerulus. While these are developing, and very soon after the stage is reached to which reference is made in the quotation, the upper S-curve elongates and becomes flexed and for a time again has the shape of an S. This Stoerk designates “secondary S,” in contradistinction to the primary 8, of which, after Bowman’s capsule is formed, there remains only the upper S-curve. In reality, as he states, there is no primary S, this being seen only in sections of this structure at this stage. He further states that the want of recognition of these two S-stages and their time relation, on the part of former observers, accounts for the contradiction which is found between his view and the views expressed by other observers as to the genesis of the different parts of the uriniferous tubules, with reference to the different parts of the S-figure. In discussing these observations of Stoerk, I desire in the first place to call attention to the fact that, while the various anlagen of uriniferous tubules from a time when they may be differentiated from the renal vesicles to a time when they present a distinct S-shape show at different stages of their development certain typic forms which are again and again met with, they after all vary in certain details both as to size and form and also as to the relative time at which certain changes in form occur. This is true not only when comparing tubular anlagen obtained from different species of animals, but also when comparing such obtained from embryos of the same species. With some reservation, the statement may be made that tubular anlagen which develop from the first few generations of renal vesicles are larger and present a slightly different form from those which develop from later generations. In the earlier stages of the development of the kidney, the branched collecting tubules are relatively far apart and the renal vesicles and tubular anlagen which develop in connection with any one system of end-branches are separated by a relatively large amount of interstitial tissue. This enables the tubular anlagen which develop at this period, when these are considered as a whole, to assume a more rounded shape than can the tubular anlagen which develop in the neogenic and subneogenic zones in the later periods of kidney development at a time when the tubular structures are more crowded and separated by a relatively small amount of interstitial tissue; consequently the tubular anlagen which develop at this period, when they are considered as a whole, do not present a rounded form, but a form which is elongated from above downward. This may be seen when comparing C and D of Fig. 4, and B and C of Fig. 6, with the two anlagen shown to the left of the two prominent branches as shown in Fig. 9, and no doubt explains, in part at least, the difference in form of early stages of tubular anlagen as given in Stoerk’s figures and the majority of those here represented. I am led to assume, both from a study of his figures and from the statements which he makes, that it is advisable to study the anlage and early developmental stages of the uriniferous tubules in as young embryos as possible, because the elements of the neogenic zone are here farther apart; that his reconstructions are made from very young embryos, while my own were made from relatively older stages—the series shown in Fig. 4 from a human embryo of the seventh month. Besides such differences in shape as here indicated, there are observed in tubular anlagen which show essentially the same stage of development, especially when these are seen in sagittal section, minor differences in shape involving the extent of the curvature of different parts and the relative size and shape and degree of differentiation of the lower S-curve, the saucer-shaped expansion of the S-shaped tubular anlage, when this is compared with its other parts. Of the series of models in my possession showing the 8§-stage of development of the uriniferous tubules, no matter whether we speak of those made from different species or of those from the same species, no two are exactly alike or even nearly so. They all show certain characteristics of form which enable a classification as to stage of development, but differ when compared in detail. This is more particularly true as concerns the form and size of the lower S-curve and its relation to the S-middle piece. The lower S-curve is developed primarily, as will be remembered, not by an invagination of the outer wall of the renal vesicle, but by a cleft which develops in a thickening of the outer wall. The extent of this cleft varies. It may not, as has been stated, extend, when first recognizable, on to the front and back surfaces of the renal vesicle and may be quite deep before the lower part of the vesicle, that part which will develop into the lower S-curve, has by extension of the cleft to any appreciable extent been separated from the part of the renal vesicle just above it, the part which will form the S-middle piece. Such a structure in reconstruction does not present the form of an S, but may do so in sagittal sections. On the other hand the cleft which appears in the outer wall of the vesicle may, almost from its beginning, extend for a distance on its front and back surfaces, in which case the lower S-curve and S-middle piece would be recognized in a reconstruction about as soon as in sections. In both cases there develops from the renal vesicle, by a deepening of the cleft and by a growth of the structure, a part which we have known as the S-middle piece and a portion known as the lower S-curve. The former develops as a short tubular segment of irregular cylindrical shape, the latter as a double-walled saucershaped structure, with concavity upwards and presenting, as seen from above or below, either an oval or more rounded or irregular triangular shape, with a distinct border at which the two layers of the structure are continuous. In the former case these parts are differentiated at a relatively later period than in the latter, when the form of the anlage is compared with its internal structure, as seen in sections. Before the S-middle piece is completely differentiated, the border or edge of the lower saucer or shell-shaped structure extends for a variable distance on to the S-middle piece and recedes gradually from this as it becomes more clearly defined. So far as my observations go, from a time when the S-middle piece may be considered as fairly well defined, — it can be traced as such into the older developmental stages and is not taken up into the lower S-curve as this changes from a saucer-shaped structure to one having a deeper concavity and presenting the shape of an irregular hemisphere, as is stated by Stoerk. This appears to be the case in tubular anlagen in which the border of the lower S-curve or saucer-shaped structure extends for an appreciable distance on to the S-middle piece, but this I interpret as due to a relatively late differentiation of the S-middle piece and not as showing that it is being taken up into the lower S-curve as in tubular anlagen, where the S-middle piece differentiates relatively early, this appears to form a definite tubular segment, which is not lost in its further development. As a matter of fact, not all of the lower S-curve, as seen for instance in a tubular anlage such as is shown in D of Figs. 3 and 4, differentiates into the double-walled concavo-convex structure, which forms, in its further development, a Bowman’s capsule; but this point shall be discussed more fully in presenting the further stages in the development. I see, therefore, no reasons for recognizing a primary S and a secondary S, as is done by Stoerk, my observations, as stated, leading me to think that the different parts of a tubular anlage which would correspond to his primary S-stage, so far as differentiated, continue as such into the stage which he has designated as the secondary S-stage, the various parts—upper S-eurve, S-middle piece, and lower S-curve—being in the latter more clearly defined than in the former; especially is this true of the S-middle piece, which becomes more clearly defined and does not disappear in the transition from the primary to the secondary S-stage, and this supposed disappearance of the S-middle piece, as the one stage passes into the other, appears to me as the crucial point in Stoerk’s argument for the recognition of these two S-stages. In making these statements, I am more especially guided by observations made on reconstructions of tubular anlagen, obtained from developing kidneys of cat embryos varying between 20 mm. and 30 mm. in length and from a human embryo of the seventh month rather than on those made of tubular anlagen developed from the first few generations of renal vesicles of relatively young human and rabbit embryos, as in the former, more generally than in the latter, the S-middle piece differentiates relatively early and consequently such tubular anlagen show at a relatively early stage an S-shape when seen in reconstruction.

Before leaving the consideration of the S-shaped stage in the development of the uriniferous tubule, brief mention may yet be made of a term which was introduced by Colberg and which has now and again been used to designate this stage. Colberg, in an article in which he attempts to controvert some statements made by Henle concerning the shape and structure of uriniferous tubules, which need not be entered upon here, gives also some observations made on the kidneys of a human embryo of the seventh or eighth month and in the course of his remarks states that the “open uriniferous tubules” (straight collecting tubules) divide in the cortex, after having given off several branches in the medulla, into four.to six side branches, which terminate in the periphery of the kidney either in club-shaped enlargements or with ends which are coiled up several times; these coiled up ends have about the same size as a fully developed Bowman’s capsule and glomerulus of a coiled uriniferous tubule. In the coiled up ends of the straight or open tubule, he was not able at first to detect capillary loops and therefore spoke of them as pseudoglomeruli. Toldt, in discussing a stage in the development of the uriniferous tubule which corresponds to the S-shaped stage, makes use of this term, although in a foot-note, he calls attention to the inappropriateness of it. Hamburger, after discussing the mode of formation of the S-shaped stage, speaks of it, as a stage designated by Colberg as a pseudoglomerulus, a term which, as Hamburger states, has been adopted by the majority of later writers and is retained by him. The term is misleading and inappropriate and need not be retained, as the mesenchyme and capillary loops found in the concavity of the lower S-curve and recognized as the anlage of the glomerulus, form at this stage only a small part of the entire tubular anlage.


The Genesis of the Different Parts of a Uriniferous Tubule from the Tubular Anlagen of the S-Stage

The.developmental changes undergone by the anlagen of uriniferous tubules, following the stage at which these present the S-shape, affect simultaneously the different parts of the S-shaped structure. In their further growth the tubular portions, embracing the upper S-curve and S-middle piece, elongate, while the bowl-shaped portion, the lower S-curve, enlarges and obtains a deeper concavity; this is accompanied by a proliferation of the vascularized mesenchyme contained within this concavity. We may consider first the changes affecting the tubular portion. This, as may be seen, is relatively fixed at its two ends, on the one hand by its attachment to the collecting tubule, on the other by its attachment to the bowl-shaped structure which contains the vascularized mesenchyme and which early forms a relatively fixed structure. Thus in its elongation it is forced to acquire secondary curvatures. Of these one is fairly constant both as to the time of its appearance and as to its location, appearing soon after the S-stage is reached and involving about the middle of the upper S-curve. The convexity of this curve is often, though not always, directed inwards toward the collecting tubule. Soon after the appearance of this curvature or coincident with it, the region of the junction of the S-middle piece and lower S-curve becomes rounded out into an arched tubule with convexity turned upwards, the lower S-curve contributing to its formation. Hence, as previously stated, not all of the lower S-curve goes to form the bowl-shaped structure. A portion of variable length in the region of its junction with the S-middle piece assumes a tubular form and with a portion of the S-middle piece forms the arched tubular segment to which reference is here made. This tubular segment may as a whole be bent forward or backward or may early acquire secondary curvatures. The region of the junction of the upper S-curve with the S-middle piece now forms a distinct loop. This region in the S-stage lies in the sagittal plane of the tubular anlage, as may be seen in D and # of Fig. 3. Coincident with the developmental changes above referred to, this portion of the tubular anlage becomes turned on its axis to a variable extent, the arm of the loop formed by the lower portion of the upper S-curve being moved backward, so that the plane of the loop now intersects a plane passing as in sagittal section through the portion representing the lower S-curve. The angle formed by these two planes varies in the different anlagen from an acute angle to nearly a right angle. These changes in form and relative position of the upper S-curve and S-middle piece seen in various degrees of development are shown in the models reproduced in #, F, and G of Fig. 4, D of Fig. 5, and D and # of Fig. 6. £#, F, and G of Fig. 3 show the appearance presented by tubular anlagen in these stages when seen in sagittal sections; E shows a tubular anlage when the tubular portion deviates but slightly from the sagittal plane, the tubule being cut through its entire length, its lumen appearing, however, only here and there, while in D the curvature of the tubule has progressed to such an extent that only a part of it falls within the plane of a sagittal section passing through the middle of the anlage; this is more marked in G@ of this figure. A comparison of these figures with #, F, and G of Fig. 4, reconstructions of the respective tubules, will assist in their interpretation. While the above mentioned developmental changes, which affect the tubular portion of the anlage, are in progress, changes affecting the lower S-curve are also to be observed. These changes consist in an enlargement as a whole of this portion and in a growing upwards of its border, thus deepening its concavity and changing it from a structure having the shape of a segment of a sphere to a hemisphere, the mesenchyme found in the concavity of the shallow structure of the earlier stage proliferating as this obtains a greater concavity, especially noticeable being an increase in the number of the capillary loops. That the epithelial portion of this structure is double-walled is evident from what has been said of its anlage and further development; its border represents the edge along which the outer wall becomes continuous with the inner wall. At about this stage of its development, its inner layer on the side toward the collecting tubule and in the region where it is continuous with the tubular portion of the anlage and at about the level of its border, develops a fold which grows outward, away from the collecting tubule, which fold in its further growth becomes continuous with the border. In sagittal sections, this fold appears as a spur and is seen in F and G of Fig. 3 and also in certain of the tubular anlagen as shown in Fig. 11. It assists in narrowing the wide opening by means of which the space (occupied by mesenchyme and capillaries) enclosed within the double-walled structure communicates with the outside. This fold further assists in differentiating more clearly this structure of hemispherical shape from the tubular portion of the anlage, in that the former now obtains a continuous border along the entire length of which the inner wall is reflected into the outer wall. This brings the attachment of the tubular portion in connection with its outer wall. The attachment of the tubular portion is always on its inner side, on the side turned toward the collecting tubule.


In a tubular anlage developed to the extent here described, there may be recognized the anlagen of the different parts of a uriniferous tubule, as these are known after its development. Briefly stated, the genesis of the different parts of a uriniferous tubule is as follows: The doublewalled hemispherical structure, which develops from the greater part of the lower S-curve, forms the inner and the outer layer of Bowman’s capsule (more correctly stated, the outer layer forms the epithelial lining of Bowman’s capsule, while the inner layer forms the glomerular epithelium); the space between the two layers, continuous with the lumen of the tubules, forms Bowman’s space; the vascular mesenchyme enclosed within this double-walled structure forms the anlage for the glomerulus, the two structures taken together forming a stage in the development of a Malpighian body or corpuscle. The region of the junction of the lower S-curve and the S-middle piece, which, as stated, differentiates into an arched tubular segment, represents the anlage of the proximal convoluted tubule. Between this arched tubular segment and Bowman’s capsule there is described a short segment, which is known as the neck of the uriniferous tubule. At this stage of development this portion of the tube is not clearly defined and is not fully differentiated until the epithelium of the portion which will form the proximal convoluted. tubule shows structural differentiation. The region of the junction of the S-middle piece with the lower part of the upper S-curve forms the anlage for the loop of Henle, that portion of the S-middle piece which does not participate in the formation of the proximal convoluted tubule forming the proximal arm of the loop, the lower part of the upper S-curve to the region where appears the secondary curvature, about its middle, as above stated, forming the distal arm of the loop, the junction of the two parts, the loop itself. The secondary curvature of the upper S-curve first to appear forms thé’ anlage of the distal convoluted portion. The upper portion of the upper S-curve from its attachment to the collecting tubule to the region where the distal convoluted portion has its anlage may be recognized as the beginning of the junctional tubule. The epithelium of the entire tubular portion of the uriniferous tubule presents at this stage of development essentially the same structural appearances. The cells throughout are of columnar shape, with a relatively small amount of protoplasm, which, unless the bleaching has been very thorough, retains to a certain extent the nuclear stain, for instance staining lightly in hemotoxylin if this stain has been used. The nuclei are relatively large, of round or oval shape, and stain relatively deeply. The lumen throughout is of about the same size and is narrow. The statements here made as to genesis of the different parts of a uriniferous tubule are based on observations made on reconstructions of developing uriniferous tubules, of stages beginning with the S-stage to a time when the metamorphosis has progressed until the different parts of a uriniferous tubule may be recognized. Attention should, however, be again called to the fact that, while models which show these stages of development present a certain similarity of form and arrangement of parts, they differ when studied in detail, as was stated in discussing earlier stages of development.


In the further elongation of the tubular portions of the uriniferous tubules, as these proceed in their development, beginning with a stage as above discussed, the portion which was above mentioned as forming the anlage of the loop of Henle needs first consideration. This portion of the tubule is found in the S-stage and some little time after, immediately above the concavity of the lower S-curve, the anlage of Bowman’s capsule, as may be seen in reproductions of reconstructions showing this stage. As this loop elongates, it either grows a little to one side (forward) and then elongates downwards toward the pelvis of the developing kidney, as shown in F of Fig. 6, or grows downward from the beginning and in doing so appears to push aside the anlage of Bowman’s capsule, which in being pushed aside is turned on its axis so that its posterior border attains a higher level than its anterior border. This is very well shown in G of Fig. 6, also, though not quite so clearly, in # of Fig. 5. While the loop of Henle is thus developing, the portion which is to form its ascending or distal limb remains in close proximity and on its inner side to the developing Bowman’s capsule, after crossing the place where this is joined to the tubular portion which forms the anlage for the proximal convoluted tubule, the descending or proximal limb of the loop lying to the inner side or slightly in front of the distal limb. The two arms of the loop are generally, from the time when they may be clearly recognized, parallel or nearly parallel; now and then the descending limb may be twisted slightly over the ascending limb, as in F of Fig. 5. In the models here reproduced, which show the early stages in the development of the loop of Henle, it will be observed that the loop of Henle grows down in front of the anlage of the Malpighian corpuscle or in front of the tubular segment attached to it. This may be accepted as a general law and holds good also for the tubules developing to the left of the collecting tubules, the ones shown in the figure all developing to the right of the collecting tubules. This statement I shall desire to amplify somewhat in discussing more fully the relations of the developing uriniferous tubule to the collecting tubules when I shall also consider Stoerk’s observations on this point. Coincident with the formation of the definite anlage of the loop of Henle, as here given, the portions of the tubule which I have designated as destined to form the proximal and distal convoluted portions also increase in length, especially the former, which grows upward and acquires two or three secondary curves. It begins at the developing Malpighian corpuscle and extends upward behind the anlage of the loop of Henle, then arches forward between the collecting tubule and the other parts of the respective uriniferous tubule, then passes downward to become continuous with the descending limb of Henle’s loop. Just before the loop is reached, it often shows a distinct flexure, which is fairly constant and characteristic, appearing also in older stages. The curvature which forms the anlage of the distal convoluted portion does not grow in length as rapidly as that part which forms the proximal convoluted portion. The curvature becomes more pronounced as development proceeds and may obtain one or more secondary bends, or may show in much older stages than here discussed a single bend. It may here be added that there is observed a considerable variation as to the relative length of this portion of a developing uriniferous tubule. Of two uriniferous tubules of apparently the same stage of development, the distal convoluted portion of one may be as long again as that of the other. This is to a certain extent true of uriniferous tubules reconstructed from embryos of the same species, more clearly seen when those reconstructed from different species are compared. Asa rule in reconstructions of uriniferous tubules showing early stages of development obtained from human embryos, the distal convoluted portion is relatively longer than in such obtained from cat and rabbit embryos. Compare for example J of Fig. 4 with H of Fig. 6, two tubules showing about the same stage of development. The distal convoluted portion of a uriniferous tubule is generally found just above the Malpighian corpuscle of the respective tubule, a relation which is fairly constant even for later stages of development, and will receive further attention in considering these. During the time in which tubular portions of uriniferous tubules develop as ahove described, the anlagen of the Malpighian corpuscles of hemispherical shape change to corpuscles of spherical shape. This is accomplished by a growing upwards and a turning in of the border of the double-walled epithelial structure representing the anlage of Bowman’s capsule and by a growing outwards of the fold which arises from its inner wall in the region of its attachment to the tubular portion, this fold being continuous with its border. In this way the opening into the double-walled structure is gradually narrowed until only a relatively small opening remains, at which, as in earlier stages, the inner wall becomes reflected into the outer wall. This opening into the double-walled spherical structure as thus developed and which may now be known as a Bowman’s capsule, is situated in its outer and upper portion. During this time, the mesenchyme and vessels recognized as the anlage of the glomerulus differentiate into a definite glomerulus, the small opening leading into the cavity of Bowman’s capsule serving for entrance and exit of the afferent and efferent vessels of the glomerulus, these being accompanied by a small amount of connective tissue. A Malpighian corpuscle of this stage of development presents essentially the same shape as a fully developed corpuscle and differs from those found in post-fetal life, aside from certain details in cell differentiation, only in being smaller. The relative degree of development of a Malpighian corpuscle and the tubular portion of a uriniferous tubule, when the extent of the development of the former is compared with the extent of the development of the latter, varies somewhat for different tubules reconstructed from embryos from the same species of animals; more so when developing uriniferous tubules obtained from embryos of different species of animals are compared. In human and pig embryos the Malpighian corpuscles develop relatively early, when considering the extent of the development of a given uriniferous tubule and may assume a nearly spherical form before the portion of the tubule which forms the anlage of the loop of Henle is clearly differentiated. This, H and I of Fig. 4 may serve to illustrate. On the other hand in cat and rabbit, developing uriniferous tubules are often met with in which the anlage of the loop of Henle is clearly made out, before the Malpighian corpuscles have progressed in development beyond the stage in which they are of hemispherical shape, with the epithelial portion in the form of a doublewalled cup, as for instance shown in # of Fig. 5, and F and G of Fig. 6.


Attention may yet be called to the fact that Malpighian corpuscles develop in about the location in which they have their anlage. Throughout the period in which new tubules are formed, new generations of tubules and Malpighian corpuscles develop outside (toward the periphery ot the kidney) of those previously formed, which makes it appear as though the Malpighian corpuscles of the older generations of uriniferous tubules sank down into the deeper parts of the parenchyma of the kidney as this developed. Herring, who has called especial attention to this fact, expresses himself as follows: “The Malpighian corpuscles seem to be fixed structures at an early period and do not move their position as do the tubules during their further growth. The early fixation seems to be due to the density of the connective tissue around the Malpighian body and it is likely that a certain part always remains constituting the framework.” The size of these structures when compared with the other portions of the tubular anlagen, the compactness of the glomerular anlage, when compared with the surrounding mesenchyme, but especially the early development of a definite vascular supply to the glomerulus, all appear to me to form factors which assist in the fixation of the developing Malpighian corpuscle.


At about the time when the developing Malpighian corpuscles have reached a stage of development in which they resemble in shape and to a certain extent in structure, fully developed Malpighian corpuscles, there is observed a cellular differentiation in that portion of the tubules which we have designated as the anlage of the proximal convoluted portion. Beginning with the region of attachment of this portion of the tubule to the Malpighian corpuscle and proceeding for the remainder of its extent it may be observed that the protoplasm of the epithelial cells increases in quantity and becomes clearer and now takes more readily a protoplasmic stain, so that in sections stained with hematoxylin and eosin or erythrosin, the protoplasm of the cells appears tinged with red.


At the same time, the nuclei take a position in the basal portion of the cells, so that the lumen becomes surrounded by a distinct margin of clear protoplasm. The nuclei also stain less deeply than in earlier stages of development and present a vesicular appearance. The lumen of this portion of the tubule, which, before the cell differentiation is observed, is relatively narrow, becomes prominent. This cell differentiation extends the entire length of the proximal portion and for a variable distance along the descending arm of Henle’s loop, as developed at this stage. This cell differentiation is shown in J and J of Fig. 3. In the former is shown about the distal one-half of the proximal convoluted portion of the tubule represented in reconstruction in 7 of Fig. 4, and its junction with the remainder of the tubule, the epithelium of which shows as yet no differentiation. In the latter is shown a loop of Henle cut through its entire length about the upper half of the descending limb of which shows an epithelium with clear protoplasm and nuclei with basal position. The proximal convoluted portion of the tubule is further seen in cross section just to the right of the upper end of the descending limb of Henle’s loop as seen in the figure; this also shows the characteristic cell differentiation. In the immediate vicinity of the Malpighian corpuscle, where the tubule becomes continuous with the outer layer of Bowman’s capsule, this cell differentiation is not so pronounced as in other parts of the proximal convoluted portion, nor do the cells of this region attain the same size as in other parts of the tubular segment; the lumen likewise is not so well developed. Consequently the tubule presents here for a short though a variable distance a smaller diameter than in other parts of the proximal convoluted portion and may now be recognized both by reason of its smaller size and by its structure as what is known as the neck of the uriniferous tubule. At this stage of development, the remaining portions of the uriniferous tubule, the greater part of the loop of Henle, the distal convoluted portion, and the junctional tubules present essentially the same structural appearance seen in the earlier stages of development.


The so-called junctional tubules of the uriniferous tubules elongate as these develop with the growth of the kidney. As has just been stated, a Malpighian corpuscle develops in about the location of its anlage; the proximal and distal convoluted portions of a tubule of which such a corpuscle forms a part, differentiate in its immediate vicinity. As the developing kidney grows in size, the collecting tubules elongate, their ends being always found just under the capsule, and as the junctional tubules are inserted at the peripheral ends of the collecting tubules (the exceptions I shall note) the collecting tubules, as they elongate, carry with them the ends of the junctional tubules; those for the uriniferous tubules first developed must then traverse the greater part of the cortex, so far as developed, in order to reach the peripheral ends of the collecting tubules. (See Stoerk, page 304.)


A detailed description of the several models,on which is based the account here given of the early developmental stages of uriniferous tubules, is obviated, it seems to me, by the number of illustrations of these stages here presented. My own observations and the conclusions reached concerning the anlage and early developmental stages of the uriniferous tubules and the genesis of the different parts of these tubules I have summarized by way of a series of diagrammatic figures grouped under Fig. 8.


Fig. 8. Semi-diagrammatic figures of the anlage and differentiation of renal vesicles and early developmental stages of uriniferous tubules of mammals. 1 and 2, anlage and successive stages in the differentiation of renal vesicles, as seen in sagittal sections; 3, section and outer form of tubular anlage before union with collecting tubule at the beginning of S-shaped stage; 4 and 5, successive stages in the development of the tubules, Bowman’s capsule and glomerulus beginning with a tubular anlage showing a well developed S-shape.


Brief mention may yet be made of the conclusions reached by former observers who have considered the genesis of the different parts of the uriniferous tubules. Toldt, who was the first to recognize clearly the S-shaped stage in the development of the uriniferous tubule, a stage in which the anlage is spoken of as a pseudo-glomerulus, does not give a clear account of the anlage of the tubular portion. I find in his account the following statement, which I shall give in his own words: ‘“ Bemerkenswerth ist ferner, dass die Windungen des Canilchens constant den der Nierenoberfliche zugewendeten, Husseren Theil des Pseudoglomerulus einpehmen, wihrend das schalenformige Ende des Canilchens stets in dem Abschnitte desselben gelegen ist, welcher nach dem Inneren der Niere zu sieht.’ (Page 134.) ‘This statement taken in connection with Toldt’s account of the development of the Malpighian corpuscle, I interpret as meaning that he regards Bowman’s capsule (and glomerulus) as developed from the lower curve of the S-shaped structure while the remaining parts of the uriniferous tubules are developed from the tubular portion of the “ pseudoglomerulus ” and not, as is now and then stated, that Toldt regards the S-shaped tubules (pseudoglomeruli) as merely the anlagen of the Malpighian corpuscles. Haycraft, in his account of the anlage of the different parts of the uriniferous tubule, makes reference to a figure (Fig. 8 of his article), which he describes as ‘(a high power view of the first formation of a urinary tubule from a primary renal vesicle,’ which figure I have interpreted as showing only a portion of a tubular anlage. He states that ‘‘ each little sprout from a renal vesicle will, in other series of older embryos, be seen to elongate, the bulging portion marked H will grow down toward the primary pelvis to form the convoluted tubules and the loop of Henle, the part at m marks the formation of the future Malpighian body.” The bulging portion marked H as shown in his figure refers to the region of the junction of the S-shaped tubular anlage with the ampulla of the collecting tubule, m marks the end of the tubule as seen in the figure. Golgi’s account of the development of the uriniferous tubules, elucidated by his well known semidiagrammatic figures of developing renal tubules of mammals is here given as presented by Minot (Page 510), leaving out the reference letters. “The different parts of the S-shaped tubule have each their fixed destiny. The end of the S (in the diagrams the lower part) receives the vascular loop, which gives rise to the bloodvessels of the future glomerulus; the lower limb of the S elongates enormously and forms the first division of the convoluted tubule including the loop of Henle; the upper limb of the S also elongates very much—though less than the lower limb—and is the anlage of the second division of the convoluted tubule; where the two join, the tubule passes close to the Malpighian corpuscle and seems to be intimately attached to it.” Except perhaps for the fact that I have differentiated more clearly the different parts of a tubular anlage of an S-shape and am thus able to give more explicitly the genesis of the different parts of a uriniferous tubule, my own account may be considered as confirming Golgi’s account as here given. Hamburger states that the first portion of the coiled uriniferous tubule to differentiate (leaving out of consideration Bowman’s capsule) is the loop of Henle, which has its anlage in that portion of the S-shaped tubule which is taken up by the bowl-shaped anlage of Bowman’s capsule (‘‘ welche eigentlich durch die von der Schale aufgenommene Biegung des S-férmigen Caniilchens vorgebildet ist’’). The portion which extends into the concavity of the lower S-curve in the region of the junction of the upper S-curve and S-middle piece, which T have also regarded as the anlage of the loop of Henle (I am not certain that I have interpreted the above statement of Hamburger correctly, as the account is not quite clear to me). He also states that the distal convoluted portion (Schaltstiick) is differentiated early, before the proximal convoluted portion (Tubulus contortus) has acquired any coils. The latter portion, he states, is developed from the third, the most distal limb of the S-shaped tubule. It should be recalled that Hamburger recognizes in the S-shaped stage (pseudogiomerulus) a bowl-shaped structure and an S-shaped tubular portion (see page 36 of this article) much as described by Stoerk for his secondary S-stage. Hamburger, in speaking therefore of the third or distal limb of the S-shaped tubule refers to the curved tubular segment which is in continuity with the anlage of Bowman's capsule; this would represent the tubular segment which develops from the region of the junction of the lower S-curve and S-middle piece, which I have also regarded as the anlage of the proximal convoluted portion. Schreiner recognizes in the S-shaped tubular anlage. essentially the same regional differentiation leading to the formation of the different parts of the uriniferous tubule as given by me, ag may be seen by a study of his Fig. 114. to which especial reference is made in his account. Stoerk’s observations on the mode of formation of the different parts_ of the uriniferous tubules need to be considered somewhat more fully, as he is the only one of previous workers who has made extensive use of reconstruction methods in the study of the subject. It will be remembered that he recognizes a primary and a secondary S-stage in the development of the uriniferous tubules. As the Malpighian corpuscle completes its development, the S-shaped tubule of the secondary S stage elongates and acquires from four to five “‘short, plump windings.” The epithelium of the tubular portion. which up to this stage, has shown the same structure throughout, now shows a differentiation, beginning with the attachment of the tubule to the outer layer of Bowman’s capsule and extending for one to two windings of the tubule. The cells here obtain more protoplasm, which becomes clearer and the nuclei assume a basal position. This cell-differentiation. as described by Stoerk, both as to the time of Its appearance and as to the region of the tubule affected is about as given by me. About this time, there develops from the coiled tubular portion a loop which grows downward over the Malpighian corpuscles to form the loop of Henle. Concerning the location of this loop, Stoerk has this to say; I use his own words: ‘Es lisst sich von vornherein durchaus_ nicht sagen, welche von den urspriinglich untereinander ganz gleich aussehenden Windungen zu diesem Anwachsen zur Schlinge bestimmt ist, solange in allen das Epithel ein dunkles ist; erfahrungsgemiss ist es meist die zweite nach dem Abgang vom Malpighischen Kérperchen.” That the portion of the tubule which is to form the anlage of the loop of Henle can be more definitely located than this statement would lead one to think I believe my models will show, especially those obtained from the cat and rabbit. In models of developing uriniferous tubules obtained from human embryos, in which the Malpighian corpuscles develop relatively early and the loop of Henle at a correspondingly later period, the portion of the tubule which is to form the loop of Henle is often not easily located; yet even from a study of these models, I have gained the conviction that the loop has its anlage in what has been termed the region of junction of the upper S-curve and S-middle piece. It is of interest to note that Stoerk states that experience shows that it is generally the second loop after the tubule leaves the Malpighian corpuscles, which forms the anlage of the loop of Henle: this corresponds, in_the majority of the models, with the region of the junction of the upper S-curve and S-middle piece and confirms, therefore, the view I have expressed.


The majority of the observers who have considered the development of the Malpighian ecorpuscle have in whole or in part followed Toldt, who considered Bowman’s capsule formed by an invagination, from one side, of the blindly ending spherical dilation of the developing uriniferous tubule, mesenchyme and capillaries participating in the invagination and forming the anlage for the glomerulus. Toldt compares this process of invagination to the pressing in of one side of a hollow rubber ball until the side pressed in comes in contact with the other side. The glomerulus develops in the concavity thus formed. Kélliker, Pye, Janosik, Nagel, Minot, Schultze, Gerhardt, and Strahl may be mentioned as accepting this view, although it is not always clear from their accounts to what extent they consider the formation of the double walled cup, the anlage of Bowman’s capsule, due to an actual invagination rather than to a process of growth on the part of the anlage of Bowman’s capsule by means of which the anlage of the glomeruJus becomes surrounded. Gerhardt, for instance, states that it is difficult to say whether the blind end of the uriniferous tubule plays an active or a passive réle in the formation of Bowman's capsule, most likely both, in that, while the capillary loops grow inward, the tubule takes an active part in the formation of Bowman’s capsule. A more correct interpretation of the process of development of Bowman’s capsule and the glomerulus is given by Herring, although he missed the anlage of the part which is destined to form Bowman’s capsule, as has been previously stated. He states that “the first appearance of the cavity of Bowman’s capsule is a narrow slit and never a vesicle in the human kidney. Toldt’s description of the driving in of one wall by capillaries is not an accurate one. At this stage there are no capillaries in the glomerulus.” ‘The further growth in size of the glomerulus may be described as an invagination, but it is not an invagination of the kind usually supposed. None of it takes place at the expense of the other side as occurs in Toldt’s illustration of the rubber ball. It is rather an increase in size by proliferation of its own constituents; the base remains in the same position and is wide at first but gradually narrows, the narrowing being brought about by the formative aetion of large cells covering it.” The formation of the lower S-curve, the anlage of Bowman's capsule, has been correctly given by Schreiner, as has been stated, and in this my own observations confirm him. By way of summary it may be stated that the two layers of the lip-shaped fold, which is separated from the outer, lower part of the renal vesicle, and which forms the anlage of the lower S-curve, are from the beginning nearly in contact, the fold presenting a slight concavity above and a_ corresponding convexity below. As _the anlage of the lower S-curve proceeds in its development, it inereases in size and assumes the shape of the bow! of a spoon, with a distinct border except where attached to the tubular portion of the anlage; the handle of the spoon, which must be thought of as bent so as to form the greater part of an S. At about this time, a small amount of mesenchyme may be found in the concavity of the lower S-curve, at first without capillaries, these growing in from without. In its further development, this double walled structure, which represents the segment of.a sphere, changes to a hemisphere by a growing upwards of the border, the mesenchyme proliferating and the capillaries increasing in number so as to fill the concavity as this develops. By a further growing upwards and a turning in of the border and by the formation of a fold on the inner layer, the hemispherical structure changes to a spherical structure, Bowman’s capsule and the glomerulus being thus completed. That Bowman’s capsule with its outer and inner layer is developed by growing upwards and ultimately by a turning in of the border of the structure with shallow concavity as seen in the lower S-curve when this is first recognized, both sections and reconstructions seem to me to show. In sections of a developing Bowman’s capsule, both the inner and outer layer for a short distance from the border and along its entire length show undifferentiated embryonic cells indicating the growing zone. This may be seen in the sketches shown in Fig. 3. This view of the development of the Malpighian corpuscle is the one taken by Stoerk, who has given correctly the main features of its development. leaving out of consideraticn the anlage of the lower S-curve, the formation of which he hardly considers, and the formation of the fold which assists in transforming the hemispherical into a spherieal structure; this fold he recognized but believes it to be developed from the middle S-piece of the primary §, which, as has been stated, he regards as being taken up into the anlage of Bowman’s eapsule, while the primary S-stage is changing into the secondary S; in my own account, IT have endeavored to show that it develops as a fold of the inner layer of the anlage of Bowman’s capsule independent of the S-middle piece.


Throughout the period in which new tubules are formed, new generations of uriniferous tubules develop outside (toward the periphery of the kidney) of those previously formed, the latter thus coming to lie relatively deeper down in the parenchyma of the kidney, as this increases in size; the tubules showing the greatest development are therefore formed nearest the pelvis of the developing kidney. To show the relative size and the shapes of uriniferous tubules and tubular anlagen developing from different generations of renal vesicles as also the relative size, shape and extent of branching of collecting tubules and their relation to the former, for a developing kidney of which the most fully developed tubules present about the size and shape of those shown in J of Fig. 4, and H of Fig. 6, these representing the oldest stages thus far discussed, I have inserted Figs. 9 and 10. In each of these figures is reproduced a model of a primary collecting duct, beginning with a region a little above its place of origin from the pelvis of the kidney and showing the successive divisions of the same to the ampullar enlargements of the end branches, together with the renal vesicles, tubular anlagen and uriniferous tubules which had developed therewith. Fig. 9 represents these structures as observed in a human embryo 3 cm. in length (embryo No. 7). In this figure, for the sake of clearness, only a part of the model is reproduced. The cut surfaces recognized by their shading represent the origin of two branches, similar to those reproduced. The collecting tubules are at this stage of development relatively large with wide lumen. The one here shown presents four successive dichotomous divisions, the end-branches showing ampullar enlargements. The pelvis of this kidney and the collecting tubules here shown are lined by a single layer of columnar cells. The figure shows further three renal vesicles, rv, five tubular anlagen in the S-stage, seen from different aspects and showing different degrees of development and two uriniferous tubules of a stage of development in which the different parts of a uriniferous tubule may be readily made out and the respective Malpighian corpuscles are nearly developed; one of these is on the rear side of the model as sketched and shows only in part, between the two prominent diverging branches. The relation of these structures to each other and to the collecting tubule is shown with sufficient clearness in the figure to obviate fuller discussion. In Fig. 10, is shown a similar reconstruction for a human embryo of 6.5 cm. length. The long diameter of the kidney from which this reconstruction was made measures 5mm. after fixation. The collecting tube reconstructed presents five and in some branches six successive dichotomous divisions. Of the four branches resulting from the second division, only one was reconstructed in full, the others are represented as cut soon after they are separated. That the collecting tubules grow in length along their entire extent as the kidney develops is shown by the fact that a greater distance intervenes between the successive branches than is shown in the former stage; the angle at which the branches meet is for the older stage more acute than for the earlier stage. During this growth in length of the collecting tubules, they obtain a smaller diameter and consequently a smaller lumen ; especially is this true of the later generations of branches. In connection with the one large branch here fully reconstructed, there are found in the model five renal vesicles and 14 tubular anlagen and uriniferous tubules in various stages of development, only a portion of which could be represented in a sketch presenting one view of the model. The complexity of this model is such that a reproduction of it can give only in a general way the shape, size, and relations of the various structures modeled and this can be shown in one figure quite as clearly as in several figures drawn from different aspects of the model. In Fig. 11 is reproduced one of the most typical sections of the series from which the model shown in the former figure was made; it falls in a plane which passes through about the middle of the model. It will serve to show the structure and cellular differentiation of certain representative tubules and tubular anlagen shown in the reconstruction; a comparison of the two figures will enable the identification of the respective parts, as represented in each figure, as they are drawn to the same scale. In the section reproduced, a collecting tubule was cut through its entire length and may be seen to end in characteristic ampullar enlargement. The epithelium lining the collecting tubules is here shown as a single layer of columnar cells which in the primary collecting duct presents the appearance of a pseudostratified epithelium. In each of the two models (Fig. 9 and 10) all of the renal vesicles, tubular anlagen and uriniferous tubules, with the exception of one uriniferous tubule, are associated with or attached to the ampullar enlargement of the end branches of the collecting tubules. The one tubule of each model having a different attachment is attached to the collecting tubule; in the model showing the younger stage of development, in the region of the second division, in the other model, in the region of the third division. I have observed this condition only in the human embryos. In the kidney of the cat and rabbit of about the same stage of development, as shown in these models, all the uriniferous tubules and tubular anlagen are attached to the ampullar enlargements of the end branches of the collecting tubules. Hamburger, who has made observations on the mode of attachment of the “coiled uriniferous tubule” to the “straight collecting tubule” on certain animals, has reached the following conclusions: He speaks of the branches of the straight collecting tubules which result from the last division of these (as seen in the fully developed kidney) as the “ terminal collecting tubules” and finds that in the beef and the mouse and generally also in the rat these terminal collecting tubules take up the ends of the coiled uriniferous tubules and only seldom (in the rat) do these terminate in the straight collecting tubules proximal to the terminal branches, while in the pig a greater number of the coiled uriniferous tubules end in the straight collecting tubules and that these further form arcades, with convexity upwards, which also serve for the insertion of the coiled tubules. The fact that at a relatively early stage in the development of the human kidney certain uriniferous tubules end in the collecting tubules proximal to their terminal branches indicates that this mode of termination obtains in post-uterine life, while the fact that in cat and rabbit embryos of about 2.5 cm. length, all the tubules end in the terminal branches would go to show that even in the fully developed kidneys of these animals, the great majority of the uriniferous tubules end in this way. Positive statements concerning this point I am at present unable to make, as I have not reconstructed collecting tubules throughout their whole extent for stages older than given in Fig. 10. Figure 9 will also serve to show that the collecting tubules in their growth and successive divisions resulting in the formation of new branches, do not in these successive divisions divide in the same plane, but with some degree of regularity in alternate planes. The configuration resulting from the last two divisions of a collecting tubule during the time when these form new branches, would resemble two Y’s the stems of which are joined to form a single stem, the four arms of which project into four quadrants of a circle. The diagram given in Fig. 12 may serve to make this clear. Uriniferous tubules develop in connection with each of the four end branches thus formed. In each of the two tubules developing in connection with the two anterior end branches, as given in the figure, the loop of Henle grows down in front of the Malpighian corpuscle and the first portion of the proximal convoluted tubule belonging to each tubule. Thus these conform to the general law as previously stated. In each of the two tubules which develop in connection with the posteriorly placed end branches, while these hold the position given in the figure, the loop of Henle grows down behind the Malpighian corpuscle and the first portion of the proximal convoluted tubule. If now the whole configuration as shown in the figure be turned through an are of 180°, thus bringing the two posteriorly placed tubules in front, these will show the same arrangement and relations of parts as was shown by the two tubules which previously occupied the anterior position; that is to say, the loop of Henle now passes down in front of the Malpighian corpuscle, while in the other two tubules, those which previously held the anterior position and now occupy a posterior position, the loop of Henle now passes down behind the Malpighian corpuscle. In stating, therefore, the general law that the loop of Henle in its development and elongation passes down in front of the Malpighian corpuscle and the first part of the proximal convoluted tubule, cognizance must be taken of the relationship of a given uriniferous tubule to the collecting tubule in which it ends. The first part of a proximal convoluted tubule, beginning with its attachment to the Malpighian corpuscle and embracing a tubular segment of variable length, passes between the loop of Henle and the collecting tubule to which said tubule is attached. If one, therefore allows the collecting tubule to which a uriniferous tubule is attached, irrespective of its other relations, to mark the posterior aspect of said tubular configuration, it may be said that the loop of Henle passes down in front of the first part of the proximal convoluted portion of the tubule, near its origin from the Malpighian corpuscle and this would also assume a position in front of the corpuscle. I can not, therefore, agree with Stoerk when he states, in connection with the statement which I have previously quoted (see page 51) in which he refers to the fact that it was not possible to state which of the four or five loops of the secondary S formed the anlage for the loop of Henle, that— and here I use his own words—“ Der Mangel an Gesetzmassigkeit ihrer Bildung aiissert sich auch darin dass sie an zwei zum gleichen Sammelrohr gehdrigen Bildungen an der einen vor, an der anderen hinter dem Malpighischen Korperchen herabfallen kann (Model L und F auf der Tafelabbildung).” Reference is here made to the downward growth in its development of the loop of Henle. In model LZ of this plate, the loop of Henle is well developed and conforms in its relations with those give in my own descriptions of this portion of the uriniferous tubule. The tubule shown in model F of this plate is so little developed that an interpretation of it is not justifiable without seeing the model itself ; I will, therefore, not attempt a discussion of it. In all the uriniferous tubules reconstructed by me, the loop of Henle is seen to pass down in front of the Malpighian corpuscle or the proximal convoluted tubule in the vicinity of its attachment to the corpuscle—and this applies to the older as well as to the younger developmental stages modeled—if by in front is meant that side of the tubular complex turned away from the collecting tubule to which a uriniferous tubule is attached as explained above and as may be seen from the diagrammatic figures given.



Fig. 9. A model of a large or primary collecting tubule, cut just above its origin from the pelvis of the kidney with the collecting tubules resulting from four successive dichotomous divisions, with three renal vesicles, five tubular anlagen in the S-shaped stage and two uriniferous tubules in early stages of development; from the kidney of a human embryo (No. 7), measuring 5 cm. in length. XxX 133. rv, renal vesicles.



Fig. 10. A model of a primary collecting tubule, cut just above its origin from the pelvis of the kidney, showing six successive dichotomous divisions. Only one of the four main branches of the second generation of branches is here shown in full, together with renal vesicles, tubular anlagen and uriniferous tubules developing in connection with this branch. From the kidney of a human embryo (No. 11). measuring 6.5 cm. X 133.



Fig. 11. A portion of a longitudinal section of a kidney of a human embryo (No. it) measuring 6.5 cm. (This section is the most typical of the series of sections used in making the preliminary drawings from which was made the model shown in Fig. 10.) XX 133. @, capsule; d, collecting tubule; pl, proximal or descending limb of Henle’s loop; m, Malpighian corpuscle with neck and a portion of proximal convoluted tubule; bc, anlage of Bowman’s capsule and a glomerulus showing fold of inner wall of capsule; dc, distal convoluted tubule; a, end branch of collecting tubule and ampulla; iz, inner zone of metanephrogenic tissue; pe, proximal convoluted tubule.



Fig. 12. Semidiagrammatic figure given to show the relations the uriniferous tubules bear to the collecting tubules and end branches as observed a short time before the middle of embryonic life. Not all the uriniferous tubules would show in such a configuration about the same degree of development as here represented. c, collecting tubule; e, end branch of collecting tubule; a, ampulla; m, Malpighian corpuscle; 7, neck; pce, proximal convoluted tubule; pl, proximal or descending limb of Henle’s loop; al, ascending or distal limb of Henle’s loop; dc, distal convoluted tubule; j, junctional tubule.

Differentiation of the Epithelium of the Loop Of Henle

We may now return for brief consideration to the stage of development represented by the tubule shown in J of Figs. 3 and 4, representing the oldest stage thus far discussed. This tubule represents one in which the Malpighian corpuscle shows a spherical form and may be regarded as fully developed; the loop of Henle is clearly recognized and presents the relations described for this portion of the uriniferous tubule, the proximal convoluted portion and about one-half of the proximal or descending limb of Henle’s loop show an epithelium with clear protoplasm and nuclei with basal position; the cells lining the remaining portions of the tubule show as yet no specific differentiation, but present the appearances shown by the epithelium lining the entire tubule at an earlier stage of development. In their further development, such tubules increase greatly in length. This growth in length affects all parts of the tubule, though not to the same extent, the proximal convoluted portion elongating more than the distal convoluted portion, the loops of the former becoming more pronounced and new ones forming. The chief increase in length is, however, observed in the two arms of Henle’s loop; this, in elongating, grows toward the pelvis of the kidney. While thus elongating, a characteristic cellular differentiation is observed in the proximal or descending limb of Henle’s loop, beginning with that region of this portion of the tubule which is marked by the termination of the cells with clear protoplasm and extending to near the loop itself—the region where the descending limb becomes continuous with the ascending limb—though never involving the loop itself. The epithelium lining this portion of the descending limb of the loop, differentiates into a flattened epithelium with flattened elliptical nuclei. The protoplasm of these cells shows very little granulation. The tubule obtains in this portion a smaller diameter than in other parts; this is more clearly seen at a later stage of development, some little time after the epithelial differentiation here mentioned may be clearly recognized. The size of the lumen of this portion of the tubule remains about the same as that of other parts. Coincident with this change of cell structure, as observed in the descending limb of Henle’s loop, the cells lining the loop itself, the ascending limb, the distal convoluted portion and for a variable distance in the junctional tubule, undergo a change in structure. The protoplasm of the cells lining these portions of the tubule increases in quantity and acquires a granular, often faintly striated appearance and shows an affinity for protoplasmic stains (eosin and erythrosin), these portions then staining more deeply than the proximal convoluted tubule and the proximal arm of Henle’s loop. The cells may be described as being of cubical or low columnar shape, with nuclei of spherical or slightly oval form and placed centrally in the cells. The diameter of these portions of the uriniferous tubules is greater than that of the proximal arm of Henle’s loop, showing the flattened epithelium, though less than in the proximal convoluted portion. The epithelium lining the different parts of a uriniferous tubule will receive further consideration in discussing more fully developed uriniferous tubules. In Fig. 13, A, is shown a model of a uriniferous tubule in which the epithelial differentiation of the different parts of the tubule, as here described, may be clearly recognized. The tubule shown represents one which measures 2.5 cm., of which just about one-half falls to the loop of Henle. (This measurement and others giving the length of uriniferous tubules are obtained from models, the length of the tubule as represented in the model being divided by the magnification at which it was made — 400). In B of this figure is shown one of the sections of the series of sections of this tubule from which the model was made; it presents with other parts, a section of the distal part of the proximal convoluted portion and its continuity with the proximal arm of Henle’s loop, showing the flattened epithelium, which is cut through its entire length to the immediate vicinity of the loop itself. The transition from the clear epithelium with basal nuclei of the proximal convoluted portion and the first part of the descending limb of Henle’s loop to the flattened epithelium of the remainder of the descending limb of Henle’s loop, is here clearly shown. The ascending limb of Henle’s loop shown in the figure does not belong to the tubule shown in the reconstruction, but to an adjacent tubule also in part reconstructed and of about the same shape and stage of development as the one shown in A of this figure, here added to enable a comparison betwen the epithelial lining of the two arms of Henle’s loop as observed at this stage of development. It may be emphasized for purposes of further discussion that the parts here designated as representing the proximal and distal arm of Henle’s loop were thus designated after reconstruction of the two tubules of which they form a part.


Fig. 13. A, uriniferous tubule from the kidney of a human embryo of the seventh month (No. 16). x 160. B, a portion of one of the sections-of the series from which the preliminary drawings used’ in making the model shown in A were made. X160. M, Malpighian corpuscle; dc, distal convoluted portion; pc, proximal convoluted portion; di, descending or proximal limb of Henle’s loop, showing flattened epithelium; c, collecting tubule; (all parts of the tubule shown in reconstruction); al’, ascending limb of Henle’s loop of a second tubule; m’, de’, dl’, portions corresponding to those designated with like letters without the accent, belonging to a second tubule.


The account here given of the differentiation of the epithelium of the two arms of Henle’s loop differs very materially from that given by Stoerk in his description of the development and cellular differentiation of this portion of the uriniferous tubule. Stoerk states that at a time when the loop of Henle is as yet very short, the clear epithelium which characterizes that portion of the uriniferous tubule destined to form the proximal convoluted portion extends to about the middle of the bend, which is to form the loop of Henle, lining therefore its proximal half, while the other half of the loop anlage is lined by the darker epithelium, which lines the remainder of the tubule. (The terms clear and dark epithelium are here used in the sense given them by Stoerk who speaks of “hellem und dunklem Epithel”). As the loop elongates, the part lined by dark epithelium grows more rapidly than the part lined by clear epithelium, so that the dark epithelium takes in the loop and extends for a variable distance into its proximal arm the clear epithelium ending, therefore, a little above the loop. He further states that “ The descending arm of Henle’s loop is therefore to be regarded as representing genetically and morphologically the end segment of the tubulus contortus of the first order, while the ascending limb represents genetically and morphologically the beginning segment of the tubulus contortus of the second order.” The descending or proximal arm of Henle’s loop to near its end is therefore, according to Stoerk, lined by an epithelium which is like the epithelium which lines the proximal convoluted portion and presents a diameter of tubule and lumen, which is also like the proximal convoluted portion, while the ascending limb, which is of smaller diameter, is lined by cells having a darker protoplasm and this not only in earlier stages of development, but also in later stages and in post-fcetal life, as is apparent from his description and also his diagram given in Fig. 27 of his article. To state clearly Stoerk’s position, I shall quote from his summary as follows:

Das Protoplasma des Kaniilchenepithels, von der Insertionssteile am_aiisseren Blatt der Bowmanschen Kapsel angefangen bis zur Umbiegungstelle der Henleschen Schleife, wird ziemlich gleichzeitig mit dem Auswachsen der Schleffe hell, das lumen dieses Kaniilchenabsch nittes erweitert. Der helle und weitere Schenkel der Henleschen Schleife ist der absteigende und nicht, wie bisher angenommen wurde, der Aufsteigende.” Stoerk also states In discussing his observations on this point that “Dieser villig einwandsfrele und ausnahmslos konstante Befund steht in direktem Gegensatze au der Darstellung im Schweiger-Seidelschen Schema und, dem seinerzeit Gesagten gemiss, auch im Gegensatze zu dem, was seither zur allgemein giiltigen Anschauung iiber das Verhalten der Henleschen Schleife geworden ist. Dass die falsche Lehre bisher keine Richtigstellung erfahren hat, ist um so verwunderlicher, als eine Reihe von allgemein bekannten. Beobachtungen so whol der normalen wie der pathologischen Histologie auf das Wiedersinnige in der Sache hatten hinweisen kénnen.

Online Editor - Translation  
These are simple Google translations of the above German text.

Das Protoplasma des Kaniilchenepithels, von der Insertionssteile am_aiisseren Blatt der Bowmanschen Kapsel angefangen bis zur Umbiegungstelle der Henleschen Schleife, wird ziemlich gleichzeitig mit dem Auswachsen der Schleffe hell, das lumen dieses Kaniilchenabsch nittes erweitert. Der helle und weitere Schenkel der Henleschen Schleife ist der absteigende und nicht, wie bisher angenommen wurde, der Aufsteigende.

The protoplasm of the cannula epithelium, from the insertion part on the leaf of the Bowman's capsule to the point of bending of the Henle's loop, becomes light at the same time as the Schleffe outgrowth, the lumen of this section of the cannula widens. The light and wider leg of the Henle's loop is the descending and not, as previously assumed, the ascending.

Dieser villig einwandsfrele und ausnahmslos konstante Befund steht in direktem Gegensatze au der Darstellung im Schweiger-Seidelschen Schema und, dem seinerzeit Gesagten gemiss, auch im Gegensatze zu dem, was seither zur allgemein giiltigen Anschauung iiber das Verhalten der Henleschen Schleife geworden ist. Dass die falsche Lehre bisher keine Richtigstellung erfahren hat, ist um so verwunderlicher, als eine Reihe von allgemein bekannten. Beobachtungen so whol der normalen wie der pathologischen Histologie auf das Wiedersinnige in der Sache hatten hinweisen kénnen.

This villainous, objectionable and invariably constant finding is in direct contrast to the representation in the Schweiger-Seidel schema and, contrary to what was said at the time, also to what has since become a generally accepted view of the behavior of the Henle loop. The fact that the wrong teaching has not yet been corrected is all the more surprising since a number of generally known ones. Observations of both normal and pathological histology could have pointed to the opposite in the matter.


I have quoted thus fully from Stoerk, as his observations (based on reconstructions) on the development and structure of the loop of Henle have led him to conclusions which are so at variance with the generally accepted views concerning the structure of the different parts of this portion of the uriniferous tubule that a clear statement of his position seemed necessary and this could best be given by making free use of his own words. That the older and generally accepted view of the size and structure of the descending or proximal limb of Henle’s loop—namely that it represents that part of the uriniferous tubule which shows the smallest diameter, as generally given in the diagrams of uriniferons tubules, beginning with the well-known one of Schweiger-Seidel, and that it is lined by a flattened epithelium—is the correct one and that Stoerk is in error when he states that this portion of the uriniferous tubule presents essentially the same diameter as the proximal convoluted tubule and is lined by a similar epithelium, is shown by those of my models which show advanced stages in the development of the uriniferous tubules. The source of his error can, I believe,*be readily shown. If one may be allowed to judge from his figures, he has reconstructed only relatively early stages in the development of the uriniferous tubules. The tubule shown as model £, as found in his plates, presents the most advanced stage figured by him. Figure 18 shows in very favorable section a tubule of about the stage of development as that shown in model LZ. In the tubule figured as seen in section, as is also apparent in references made to it in the text, the clear epithelium found in the proximal convoluted portion extends for about half the length of the descending or proximal arm of Henle’s loop. This portion of the tubule has also a greater diameter than is shown by the greater part of the remainder of the tubule figured by him, the latter part being lined by the darker epithelium. The tubule shown in Fig. 18 of his article presents about the same stage of development and cellular differentiation as that shown under J of Fig. 3 of this article, and this tubule was selected as showing a stage of development just prior to that in which the epithelium of the proximal and distal arms of Henle’s loop shows the specific differentiation described for them. In A and B of Fig. 13, in which is represented a tubule showing a stage in which the epithelium of all its parts shows characteristic differentiation and represents a stage a little more advanced than the oldest stage figured by Stoerk, it may be clearly seen that that portion of the descending limb of Henle’s loop which in J of Fig. 3 or in Fig. 18 (Stoerk’s) shows the darker epithelium, differentiates as the loop elongates, into the flattened epithelium characteristic of the greater part of the descending limb of Henle’s loop. Stoerk, in formulating his conclusions relating to the shape and structure of the descending and ascending limbs of Henle’s loop makes use of data gained from a study of uriniferous tubules representing stages of development in which the epithelial differentiation is not as yet complete in all parts of the tubules, notably in the descending and ascending limbs of Henle’s loop. It may readily be seen how from such insufficient data, he would be led to the conclusions drawn. If the loop of Henle in either of the tubules shown in J of Fig. 3 or in Stoerk’s Fig. 18 were drawn out to form a long loop of Henle, retaining the structure given them in the figures, the result would be a tubule in which the descending limb of the loop would be lined by a clear epithelium to near its end, one which would show a greater diameter than the ascending limb, which would be lined by a darker epithelium. This is what he has done and was thus led to the error he has committed. That he is not justified in assuming that the uriniferous tubules presenting the stages represented in his Figure 18 and model Z show the structure and cellular differentiation of fully developed uriniferous tubules, may be seen, J believe, in A and B of Fig. 13 and is also shown by my other models showing more advanced stages of development. It may, therefore, again be stated that reconstructions of proper stages in the development of uriniferous tubules show that the descending limb of Henle’s loop is lined by a flattened epithelium and presents a smaller diameter than the ascending limb, which is lined by a cubical or short columnar epithelium, confirming thus the generally accepted view of the size and structure of the two arms of Henle’s loop.

Peculiarities of Form Presented by the First Developed Uriniferous Tubules

Before leaving the discussion of the earlier stages in the development of the uriniferous tubules, mention may yet be made of differences in development presented by tubules which develop from the first few generations of renal vesicles, when compared with those which develop from the later generations. Such differences of development are expressed mainly in the relative degree of development shown by the different parts of the tubules which are first formed, when these are compared with those which develop later. It should, however, at the beginning be stated that such differences in development as shall here be mentioned are not of such a character as to form exceptions to the statement that the uriniferous tubules which develop from the various generations of renal vesicles present essentially the same developmental stages as have been given in the preceding pages. As has previously been stated, tubules which develop from the earlier generations of renal vesicles present in the S-stage and for some little time after, when their configurations are taken as a whole, a more rounded form than do those which develop from later generations of renal vesicles. This difference in form when the one type is compared with the other, is also observed in tubules of the respective types in which the anlagen of the different parts of the uriniferous tubule may be clearly made out in that the first developed tubules present at this stage, an irregularly spherical mass when the developing Malpighian corpuscle and the tubular complex are taken together and considered as a whole. (See H and F of Fig. 5). The tubules of similar stage of development derived from later generations of renal vesicles, likewise congidered, form a more elongated mass. (See G of Fig. 6). This, as has been stated, is in part at least due to the fact that during the earlier stages of development of the kidney, the tubular structures are relatively far apart and are surrounded by a relatively large amount of mesenchymal tissue and may thus in growth and elongation expand in all directions, while in later stages of development the tubular structures are in much closer proximity, separated by only a relatively small amount of mesenchymal tissue; this juxtaposition to surrounding tubules influencing the direction of their growth. In their further development, tubules which are developed from the first few generations of renal vesicles are characterized by a relatively early and marked elongation of those portions of the tubule destined to form the proximal convoluted portions, so that this portion forms a prominent part of the entire tubule for a certain period of its development, as may be seen in reconstructions and in sections. The epithelium lining this portion of the tubule as this elongates differentiates into one showing cells with clear protoplasm and nuclei in basal position as described for the proximal convoluted tubule. The loop of Henle of these tubules for a certain period of their development remains relatively short, when their length is compared with that of the proximal convoluted portion. These tubules generally show throughout, but especially in their proximal convoluted portions, a greater diameter than tubules which develop later, the lumen of the proximal convoluted portion being especially wide. Their Malpighian corpuscles are also relatively large. In tubules which develop from renal vesicles that follow the first few generations of these, the loop of Henle elongates at a relatively early period of their development so as to form a prominent portion of the tubule at a time when the proximal convoluted portion shows only a few relatively short coils; the proximal and distal convoluted portions taken together form thus a smaller mass than is formed by similar portions of the tubule first formed at a time when each type presents a loop of Henle of about the same length. This gives the two types of tubules when seen in reconstructions a characteristic form, and enables a distinction between them. ‘To characterize these differences of form more clearly, reference is made to the models reproduced in Figs. 14 and 16. In C and D of Fig. 14, are shown two tubules reconstructed from the kidney of a rabbit embryo measuring 3.5 cm. They are from the layer of tubules situated nearest the pelvis of the kidney and are therefore of those which are first formed. Attention is called to the length and thickness of the proximal convoluted portion of each of these tubules and to the relative shortness of the loop of Henle. In A and B, are shown two tubules, presenting different stages of development, reconstructed from the same kidney and are representative of tubules the Malpighian corpuscles of which are situated nearer the periphery of the kidney and were therefore differentiated later than the Malpighian corpuscles and tubules of which C and D are types. In the second type of tubules, the loop of Henle is relatively long, when compared with the proximal convoluted portion; in A, of about the same length as the loop of tubules C and D, while the proximal convoluted portion of tubule D measures 1.5 mm., of C, 1 mm., and of A only 0.5 mm. The difference in shape presented by the two types of tubules is apparent from the figures. The Malpighian corpuscles and coiled portions of the uriniferous tubules situated nearest the pelvis of the kidney form a distinct layer, just above the mesenchyme which surrounds the pelvis, which is readily recognized in kidneys of embryos of about the middle of fcetal life; the sections of proximal convoluted portions of these tubules form the greater part of this layer in such preparations. The appearance presented by a section of the kidney at this stage of development is shown in Fig. 15, in which is given a portion of one of the sections of the series of cross sections from which the models shown in Fig.14 were made. The sections of the tubules and Malpighian corpuscles designated by the letter a, belong to a tubule of the type shown in C and D of the previous figure; tubule b is the one shown in A of that figure. In the remainder of the section may be seen renal vesicles and tubular anlagen in various stages of development. This portion of the sections which constitutes the neogenic and subneogenic zones, stains more deeply than the portion containing the well developed proximal convoluted tubules; these, by reason of the fact that they are lined by a differentiated epithelium (as previously described), the protoplasm of the cells of which stains faintly in eosin and erythrosin, form a zone which stains less deeply than the more peripheral portions containing the tubular anlagen with undifferentiated epithelium of an embryonic character. In Fig. 16, are shown two uriniferous tubules, 4, from the kidney of a cat embryo of 4 cm. length; B from the kidney of a cat embryo of 6 cm. length; both are representative of types of tubules found nearest the pelvis of the respective kidney and show more advanced stages of development than are shown by tubules C and D of Fig. 14. Tubule A measures 3.75 mm., of which 1.9 mm. falls to the proximal convoluted portion, the entire loop (ascending and descending limbs) measuring .75 mm. The length of tubule B is 5 mm., of this 2.65 mm. falls to the proximal convoluted portion and 1.5 mm. to the entire loop of Henle. In these tubules, as is no doubt apparent from the figures and measurements given, the proximal convoluted portions form the more prominent part, a little over half the length of the entire tubule. Similar observations may be made on the kidneys of human embryos of about the third and fourth month; although the differences of size and shape of the tubules which develop first when compared with those which develop later are not so marked in the human embryo as in those of the cat and rabbit; they are, however, of similar character and of sufficient degree to merit recognition.


Fig. 14. Tubules from the kidney of a rabbit embryo of 3.5 cm. length (No. 8). X 100. m, Malpighian corpuscle; pc, proximal convoluted portion; dc, distal convoluted portion; di, descending limb of Henle’s loop; al, ascending limb of Henle’s loop; j, junctional tubule; C and D are representative of the first few generations of tubules. A and B of later generations.


Fig. 15. A portion of a cross section through the kidney of a rabbit embryo of 3.5 cm. length (No. 8). x 100. a, sections of proximal convoluted portion and Malpighian corpuscle of a uriniferous tubule representative of the first formed tubules of this kidney; a’, section of ascending limb of Henle’s loop of the same; d, tubule shown in A of Fig. 14, representative of a later generation of tubules; ct, collecting tubule; c, capsule.


Fig. 16. Two uriniferous tubules, A, from kidney of cat embryo of 4 cm. length (No. 6); B, from kidney of cat embryo of 6 cm. length (No. &). x 100. <A’, B’, figures showing the course of the proximal and distal convoluted portions of the two tubules; the tubule representing the distal convoluted portion is shaded; m’, Malpighian corpuscles.



In Fig. 17, are represented three stages in the development of uriniferous tubules as observed in the pig embryo. My observations on the development of uriniferous tubules in pig embryos are not as yet complete, owing to the lack of suitable material showing the older stages of development. They have for this reason not received more than casual mention in the preceding pages. A fuller treatment is reserved for another contribution, in which the development of the collecting tubules, more particularly the development of the so-called arcades of the collecting tubules discussed and figured by Von Ebner (p. 1105) will receive consideration. The tubules presented in Fig. 17 have been added, as they illustrate very clearly the fact that the first few generations of tubules of kidneys of pig embryos show a relatively very early development of the proximal convoluted portions and of the Malpighian corpuscle, while the loop of Henle develops at a relatively late period; tubule B, for instance, has attained a length of 1.5 mm. and presents a fully developed Malpighian corpuscle, at a time when the bend which is destined to form the loop of Henle (recognized by the fact that the differentiated epithelium of the proximal convoluted portion extends to nearly the top of the bend,) may just be made out. In tubule C, the portion which is recognized as the anlage of the loop of Henle presents a number of coils instead of being a relatively straight limb—an appearance which I have observed only in pig embryos. It may here be stated that the formation of the renal vesicles and the differentiation of the S-shaped stage of the uriniferous tubules is for pig embryos essentially the same as for cat, rabbit, and human embryos, as discussed and figured in these pages. Hamburger’s observations are of interest in this connection. In discussing the differences in form presented by the anlagen of uriniferous tubules in younger and older stages, he states that “the size of the anlage is different in younger than in older embryos and for the same stage of development it will generally be found that they are larger in the former than in the latter; especially is this true of the pseudoglomeruli, which are especially large in young embryos.” This, as may have been seen, I have confirmed, adding that they differ, not only in size, but also in shape. He further describes characteristic differences in the development of uriniferous tubules in simple kidneys when compared with those of lobulated kidneys. To quote further: “In animals with simple kidneys (mouse, rat,) the loop of Henle attains considerable development before the Bowman’s capsules become closed so as to form a sphere and this is as true of the first formed anlagen as for those which develop later. In animals with lobulated kidneys (‘zusammengesetzten Nieren ’) I have found a different condition; in them, the coiled tubules first formed attain considerable length and the Malpighian corpuscles, full development, before a loop of Henle may with certainty be discerned ; the later development, however, is as in simple kidneys.” His description of the development of the earlier generations of uriniferous tubules, as observed in embryos of animals with lobulated kidneys (human, pig,) coincides with that here given. In embryos of the cat and rabbit (animals with simple kidneys), I have also observed, as has been stated, a difference between the tubules first formed and those which develop later. As I have not reconstructed the uriniferous tubules of embryos of the mouse and rat, I am not in a position to judge Hamburger’s observations as concerns these; he is, however, in error when he generalizes from such observations. He further states that “In young embryos of species with lobulate kidneys (human, pig, beef), the most fully developed Malpighian corpuscles are absolutely larger than in older embryos and this is also true of the diameter of the tubuli contorti. In animals with simple kidneys (mouse, rat), this not the case.” In this also, my own observations do not confirm him, as in embryos from both types of animals 1 have found the Malpighian corpuscles and the proximal convoluted portions (tubuli contorti) of the first formed tubules larger than of those which develop later; in the rabbit, this is especially so. (See Fig. 14.) In a discussion of his observations, Hamburger states that it may be possible that in tubules showing early development of the coiled portions and Malpighian corpuscles with absence of a distinct loop of Henle, these may develop as the kidney development proceeds. “ Since without doubt, however, the first generation of coiled tubules of lobulated kidneys degenerates, the supposition is permissible that it is particularly the atypical tubules that disappear; conclusive evidence of this, J am however unable to present.” Riedel (I quote from Hamburger) who also recognized the large size of the Malpighian corpuscles and tubuli contorti of the first formed tubules, states that these become smaller as development proceeds. Kélliker, whose description is based largely on rabbit embryos, quotes Riedel (page 952) as describing a degeneration of the Malpighian corpuscles and tubuli contorti first formed, for which he states there is no evidence. Emery, on the other hand, who studied the development of the kidney in goat embryos, states that he did observe evidence of a breaking down of the first formed tubules. Hamburger attempts to harmonize the conflicting views of Kélliker and Emery by stating that in embryos of animals with simple kidneys, there is no evidence of a breaking down (zu Grundegehen) of the first formed tubules, while in embryos of animals with lobulated kidneys, it is the atypical tubules which atrophy and disappear. My own observations lead me to say that neither in embryos of animals with simple kidneys nor in those with lobulated kidneys have I obtained evidence which would lead me to conclude that any of the uriniferous tubules atrophy and disappear in the course of development. Tubules with relatively short loop and well developed Malpighian corpuscles and proximal convoluted portion, I have observed in embryos of animals with simple and with lobulated kidneys; in such tubules, as will be stated in presenting the more advanced stages of development of uriniferous tubules, the loop of Henle elongates at a relatively late period, developing and differentiating as do the loops of other tubules. I agree, therefore, with Minot when he states: “Some authors have maintained that there is an atrophy of some of the tubules of the feetal kidney, but I agree with Golgi in believing that of this there is no valid evidence.” In offering an explanation for the difference in the development of the first generation of uriniferous tubules, when these are compared with those which develop later, which difference may be characterized as consisting of a relatively early development of the Malpighian corpuscles and the proximal convoluted portions and a relatively late development of the loop of Henle of the former when compared with the latter, attention may be called primarily to the simple mechanical condition which prevents an elongation of the loop of Henle of the first formed tubules. The Malpighian corpuscle and tubular portion which are first formed develop near the developing pelvis of the kidney, the former being separated from the latter by a relatively narrow zone of mesenchyme. As the tubules proceed in their development, their loops of Henle soon reach the epithelium of the growing pelvis and the denser mesenchyme immediately surrounding it. The loop of Henle of tubules C and D of Fig. 14 and A and B of Fig. 16 reach to the pelvis of the respective kidneys. The ends of such loops are often seen bent to one side or the other, as though attempting to avoid the obstruction which prevents their further elongation, and they are often slightly folded and twisted, the end of the loops being bent so as to project toward the periphery of the kidney, as for instance in tubule 4 of Fig. 16. Sections of developing kidneys of pig embryos of about 2.5 to 5 em. length (the oldest stage available for me) show this in a very characteristic manner. In the series of sections from which the model shown in C of Fig. 17 was made, the Malpighian corpuscle was separated from the pelvis of the kidney by a distance which is about two-thirds the length of the diameter of the corpuscle; a large collecting tubule which opens into the pelvis by a funnel-shaped expansion is nearly in contact with the coiled tubular segment designated in the figure as the descending limb of the loop. There is obviously here no opportunity for the formation and the elongation of a loop with relatively straight and nearly parallel limbs. The fact that so little mesenchyme separates the tubules and the Malpighian corpuscles from the pelvis of the kidney, and the shortness of the loop of Henle at a time when the proximal convoluted portions are well developed, also the fact that the loops of Henle, so far as developed, are not present in the form of straight tubules, but as coiled tubules, so that only cross or oblique sections of them are obtained, give to sections of kidneys of pig embryos of these stages a very characteristic appearance, resembling somewhat the appearance presented by sections of the mesonephros, and making it easy to distinguish them from sections of kidneys of cat, rabbit, and human embryos of corresponding stages of development.



Fig. 17. Three uriniferous tubules from kidneys of pig embryos. X 133. A and C, from embryo of 2.8 cm. length (No. 8). The latter is representative of the first generation of tubules, situated nearest the pelvis and is shown from the Malpighian corpuscle to the first coil of the distal convoluted portion; the former represents a much less developed tubule, one situated nearer’ the periphery of the kidney; B, one of the most fully developed tubules from the kidney of an embryo of 2.4 cm. length. m, Malpighian corpuscle; pc, proximal convoluted portion; dc, distal convoluted portion; 7, anlage of loop of Henle; dl, of descending limb; al, of ascending limb; d, collecting tubule.


The fact that the anlagen of tubules which are first formed are relatively far apart, the growth of the tubules developing from them being thus for a time not materially interfered with, may be mentioned as a possible reason for the early development and elongation of the proximal convoluted portions of these tubules, certainly an explanation of the fact that these tubular portions are coiled more in the horizontal plane than similar portions of tubules which develop later.


Malpighian corpuscles of a stage of development in which they present the form and cellular differentiation shown by these structures in postfoetal life, and proximal convoluted portions of tubules in which the epithelium has become differentiated so as to present the structural appearances presented by it in more fully developed tubules, even though such corpuscles and tubular segments are found in early stages of kidney development, may be thought to have assumed functional activity. If may be suggested, therefore, that in the uriniferous tubules which are first formed, those portions which are especially concerned with the function of excretion are rapidly differentiated to perform this function, while the other portions which are not especially concerned with the function of excretion are developed more slowly. Although there is as yet no unanimity of opinion as to the special functions to be ascribed to the different parts of a uriniferous tubule, assuming that the differences of shape and structure observed in the epithelium lining the different parts of the uriniferous tubules postulates a difference of function for the several parts lined by the especially differentiated epithelium, the generally accepted view is that the Malpighian corpuscles and the proximal convoluted portions of the uriniferous tubules are more particularly concerned with the function of excretion. The assumption, therefore, seems justified that it is for this reason, and not alone owing to mechanical conditions, that the Malpighian corpuscles and especially the convoluted portions of the first-formed uriniferous tubules are developed and differentiated relatively early, so as to enable the permanent kidney, at an early stage in its development, to assume an excretory function.


Late Stages in the Development of Uriniferous Tubules

The further growth and development of uriniferous tubules, after a stage in which all the parts show a characteristic differentiation (as for instance seen in the tubule of Fig. 13) consist primarily in an elongation of the tubular portion, this affecting all its parts, but especially the loop of Henle. The data gained by me concerning the later stages in the development of uriniferous tubules are confined to a large extent to those obtained from observations on older embryos of cat and rabbit, the kidneys of which are of relatively simple type, with only one Malpighian pyramid. The disposition of the collecting tubules and other tubular elements of the medulla of such a kidmey is such that both in series of cross and longitudinal sections a certain few will be found in which the plane of section is parallel or very nearly parallel to certain of the collecting tubules and loops of Henle. Nearly every such series will show here and there a loop, one or the other arm of which is cut for nearly its entire length, and, by using this as a starting point, I have generally succeeded in tracing out the remainder of the tubule in question. In the human kidney of the later periods of foetal life, the conditions are complicated by reason of the fact that the cortex is divided into a number of primary and secondary lobules, and even when one lobule is used for sectioning J have found it quite impossible to orient the block in such a way as to obtain long segments of either of the two arms of the loop of Henle, especially for the upper regions of the medulla. In this region the tubular elements very generally appear in oblique section and are separated in the kidneys of human embryos of the 8th and 9th months by a relatively small amount of interstitial tissue, which makes the tracing of a single tubule through this region and, as is often necessary, through a long series of sections a matter of difficulty. From a number of partial reconstructions which were made, I am led to believe that the observations made on uriniferous tubules of the older embryos of cat and rabbit (especially the former) may be accepted as presenting the conditions shown by uriniferous tubules of human embryos of the later months of fetal life. My observations on the later stages of development of uriniferous tubules, I shall present by giving a brief description of certain tubules showing these, which have been reconstructed in full and which are here figured. In Fig. 18 are shown two uriniferous tubules, the Malpighian corpuscles of which are situated in about the middle zone of the cortical portion of the kidneys from which they were reconstructed and may, therefore, be taken as representative of tubules which were differentiated after the first formed tubules of the respective kidneys. Tubule A is from the kidney of a cat embryo obtained a few days before birth. The length of this tubule is 4.1 mm., of which 1.75 mm. falls to the proximal convoluted portion, 1.65 mm. to the entire loop of Henle (the measurement here beginning and ending with the level of the lower border of the Malpighian corpuscle) and .? mm. to the distal convoluted portion and the junctional tubule. As may be seen from the figure, more clearly from the key, the proximal convoluted portion presents one prominent primary loop, which extends toward the periphery, and numerous secondary loops. The distal convoluted portion is practically enclosed within the coil formed by the proximal convoluted portion. The proximal or descending arm of the loop, as the sections show, is lined nearly throughout—from a little below the level of the Malpighian corpuscle to near the loop proper—by a flattened epithelium, while the distal or ascending arm, with the loop itself, presents a slightly larger diameter and is lined by a cubical epithelium, and on reaching the coiled portion passes in front of the first part of the proximal convoluted portion, near the corpuscle. Tubule 8 of this figure is from the kidney of a rabbit embryo of 6.5 em. length. Its length is 4.2 mm., of which 1.6 mm. falls to the proximal convoluted portion, 1.8 mm. to the entire loop of Henle, and .8 mm. to the remainder of the tubule. The disposition of the various parts of this tubule is similar to that shown by tubule A, except that the distal convoluted portion is more exposed. Attention should be called to the proximal arm of Henle’s loop. About the upper half of this presents the same diameter (and structure) as the proximal convoluted portion. This portion represents the so-called spiral portion of Schachowa or the end piece (end segment) of Argutinski, and is in reality the distal segment of the proximal convoluted portion. It does not, so far as I have been able to observe, form a spiral; the term spiral tubule is therefore inappropriate. About the lower half of this loop presents the characteristic shape and structure of the descending arm—small diameter and lined by flattened epithelium. The transition from one to the other is clearly shown in the figure. The loop itself, as well as the ascending limb, presents a larger diameter than the thin portion of the descending limb and is lined by a cubical epithelium. It may here be stated that this tubule presents in a very characteristic way the shape, arrangement, and structure of the several parts found in tubules, the Malpighian corpuscles of which are situated in a zone of the cortex, above that occupied by corpuscles and coiled portions of the tubules first formed, which are nearer the medulla.



Fig. 18. A, uriniferous tubule from kidney of cat embryo obtained a few days before birth (No. 9); B, tubule from kidney of rabbit embryo 6.5 mm. in length (No. 13). X100. A’, B’, keys giving course of coiled portions of tubules, distal convoluted portions shaded. m, Malpighian corpuscles; pc, proximal convoluted portions; es, end segment; di, descending Hmb, al, ascending limb of Henle’s loop; j, junctional tubule.



Tubule A, shown in Fig. 19, represents one of the most fully developed tubules from the kidney of a rabbit embryo 6.5 cm. long. It has a length of 5.8 mm., of which 2.2 mm. forms the proximal convoluted portion, 2.75 mm. the entire loop of Henle, and a little less than 1 mm. the remainder of the tubule. This tubule I regard as one which in earlier stages of development would have shown a relatively long proximal convoluted portion, with a short loop of Henle—a so-called atypical tubule (Hamburger)-—and for the following reasons: The loop of Henle reaches to near the pelvic epithelium, being separated from it by only a small amount of interstitial tissue; its Malpighian corpuscle is situated in the deepest portion of the cortex, just above its junction with the developing medulla; the prominent coils of the proximal convoluted portion have a more horizontal position and are, therefore, spread out more in a lateral direction than would be true for tubules which develop later, in which the prominent coils of the proximal convoluted portion are more prone to grow in a perpendicular direction, toward the cortex. As I have seen no evidence of the atrophy of the first formed tubules—so-ca]led atypical tubules—with relatively short loops of Henle—it is assumed that this loop elongates as the medulla develops. The distal convoluted portion of this tubule lies upon—in front of, as shown in the figure—the coil complex formed by the proximal convoluted portion, the course of which may be ascertained by a study of the key A’. The descending limb of the loop is lined almost throughout by a flattened epithelium and presents a comparatively small diameter. The end segment is relatively short, forming only a small part of the limb. The loop itself and the distal limb have a diameter which is just about three times that of the greater part of the descending limb. The sharp bend shown by the ascending limb, just before the Malpighian corpuscle is reached, is due to the fact that a relatively large arterial branch occupies the space just beneath the corpuscle, the distal limb arching partly over this to reach the vicinity of the corpuscle. For this reason also the upper end of the proximal limb is separated by a greater distance from the Malpighian corpuscle than may be considered typical. With these exceptions, this tubule may be regarded as presenting in a very characteristic manner the shape and arrangement of the different parts of a uriniferous tubule, the Malpighian corpuscle of which is situated in the deepest portion of the cortex, thus of the first few generations of uriniferous tubules. Tubule B of Fig. 19 represents one of the most fully developed tubules of the kidney of a rabbit killed the first day after birth. Three exceedingly fortunate sections of the series of cross sections 5 » thick, into which one of the kidneys was cut, contained nearJy the entire length of the proximal limb of its loop. The model of this tubule measures from the tip of the loop to where it ends in the collecting tubule four feet and four inches. On completing the reconstruction, the tubule proved to be one presenting a not quite typical arrangement of the coils of the proximal convoluted portion, these forming a configuration which is too open and too much in one plane. The cause of this is not readily made out at the stage of development here presented. The tubule shown in C of Fig. 14 presents almost the same relations of its parts, and for that tubule it is evident that the somewhat atypical form assumed is due to the fact that its juxtaposition to other and slightly larger tubules is such that for purely mechanical reasons, on growing and elongating presumably in the direction of least resistance, its coiled portion was forced to assume the form presented by it. The Malpighian corpuscle of tubule B is found in the second tier of corpuscles, while its loop of Henle extends nearly to the pelvis of the kidney. Its entire length is 7.8 mm., of which the proximal convoluted portion forms 1.85 mm., the entire loop 4.8 mm., the distal convoluted portion 0.55 mm., and the remainder- of the tubule 0.57 mm. The arrangement of the different parts of the tubule is such that its entire course may be followed in the figure; a key is therefore dispensed with. The tubule presents only a short end segment, the greater part of the descending tube to near the loop itself forming a tubule of small diameter (12 to 15), lined throughout by a flattened epithelium, while the ascending limb with the exception of the lower one-sixth is lined by a cubical epithelium with faintly striated protoplasm. It is evident from the character of the epithelium which lines the loop itself and the lowest part of the two limbs (cells of embryonic character with relatively large, deeply staining nuclei) that this portion of the loop is elongating to keep pace with the enlarging and elongating Malpighian pyramid.



Fig. 19. Tubule A, from kidney of rabbit embryo (No. 13) measuring 6.5 cm. X80. Tubule B, from kidney of rabbit one day old (No. 14). x 40.


The tubule shown in Fig. 20 was reconstructed from the kidney of a cat embryo obtained a few days before birth; the model presents a length of four feet. The tubule itself measures almost exactly 9 mm.; 2.4 mm. belonging to the proximal convoluted portion, 4.85 mm. to the entire loop of Henle, 1.1 mm. to the distal convoluted portion, and 0.55 mm. to the junctional tubule. This tubule I regard as showing in a very typical manner the shape, arrangement, and relations of the different parts of a uriniferous tubule, especially one the Malpighian corpuscle of which is ‘situated in the deeper portion of the cortex. The course of the proximal convoluted portion may be ascertained from the key (unshaded tubule). The curvatures of this part, as shown in the key, are, for the sake of clearness, not so pronounced as in the actual model, but are drawn with sufficient accuracy to give correctly the course of this part of the tubule. The distal convoluted portion presents two prominent loops and in its upper portion two smaller loops, in which portion there may also be observed irregularities in the diameter of the tubule. The shaded portion of the key gives the course of this portion of the tubule. The coils formed by it lie over—or in front of, as shown in the figure—the coil complex formed by the proximal convoluted portion, the prominent loop being found a little above the Malpighian corpuscle. The proximal limb of Henle’s loop presents almost throughout a small diameter and is lined in this portion by the characteristic flattened epithelium. The end segment is short and presents in a typical manner the transition in shape and structure of the tubule as found in the proximal convoluted portion to that seen in the descending limb. The loop itself and the ascending arm have a diameter which is about twice that of the greater part of the descending limb and are lined by a cubical epithelium. The ascending limb reaches the coil complex in the immediate vicinity of the Malpighian corpuscle with which it is practically in contact for about one-third of the latter’s circumference. The proximal limb leaves the coil complex in close relation with the upper end of the distal limb, therefore very near to the Malpighian corpuscle. The lower end of the loop of this tubule reaches to the pelvis of the kidney, being separated from its epithelium by only a small amount of interstitial tissue.




Fig. 20. Uriniferous tubule from kidney of cat embryo obtained a few days before birth (No. 9). X30. m, Malpighian corpuscle; mn, neck; pc, proximal convoluted portion; es, end segment; di, descending limb; al, ascending limb of Henle’s loop; dc, distal convoluted portion; /, junctional tubule.


In the tubules shown respectively in B of Fig. 19 and in Fig. 20, the Malpighian corpuscle is fully developed and the proximal and distal convoluted portions may be regarded as also fully developed and as having attained the size and for all practical purposes the length to which the tubular portions grow. This statement is based on the measurements made on uriniferous tubules—especially those which are developed earliest—at different stages of their development. The measurements given below show that the proximal convoluted portions at a relatively early stage in their development attain a length which is about that presented by these tubular segments in later stages of embryonic development or at birth. The following summary of certain of the measurements previously given presented in the form of a table may serve to substantiate this:



S | 63 s z a ° ; Ens ness Se é TUBULE. OBTAINED FROM. aE B Ss SH] 256 Loop BEE |EZES) 8s BF 498) ar i Fig. 16, A Cat embryo, 4 cm. 3.75 mm. (1.9 mm. | ...... | 75 mm. Fig. 16, B | Cat embryo, 6.5 cm. 5 mm. 2.65 mm.| ...... 1.50 mm. Fig. 20 Cat embryo just before | 9 mm. 2.4 mm. (1.1 mm. | 4.85 mm. birth Fig. 14, D Rabbit embryo, 3.5 cm. 2.9 mm. 1.5 mm. | ...... | see, Fig. 19, A Rabbit embryo, 6.5 cm. 5.8 mm. (2.2 mm. | ...... 2.75 mm Fig. 19, B Rabbit at birth 7.8 mm. 1.85 mm.| .55 mm. | 4.8 mm


The data given in the table will show, I believe, that the elongation of the uriniferous tubules, after a certain period in their development, is to a large extent due to a growth in length of the loop of Henle, the proximal convoluted portion of each tubule attaining at a relatively early period in its development approximately the length shown by this tubular segment in fully developed tubules.


To show how much of a single uriniferous tubule, representing a stage in which the Malpighian corpuscle and proximal and distal convoluted portions may be regarded as fully developed, is contained in a selected section of a series of sections containing the whole tubule, I have inserted Figs. 21 and 22, in each of which the several parts of a single uriniferous tubule are sketched darker than the remaining portions of the sections reproduced. In Fig. 21, A and B, are reproduced portions of the cortex of two sections from the series of sections from which tubule B of Fig. 19 was reconstructed. A comparison of this figure with that showing the reconstruction will show that the plane of section was at tight angles to that in which the model is reproduced. A line drawn through the middle of the Malpighian corpuscle, and the proximal convoluted portion (see B, Fig. 19) shows the location of the section, a portion of which is shown in B of Fig. 21. In this section the Malpighian corpuscle, the proximal convoluted portion soon after leaving the corpuscle and two arms of a loop of it as it comes back over the corpuscle are met with. Their relation to each other and to the surrounding structures may be seen from the figure. In A of the figure is shown a portion of the 13th section further on in the series. This section passes practically through the entire length of the junctional tubule (leading to the periphery of the cortex) which will indicate its position in the model; also through the coils of the distal convoluted portion, which is cut in cross section four times and through a long and a short loop of the proximal convoluted portion, escaping the Malpighian corpuscle. In Fig. 22 is shown a portion of the cortex—about the lower one-half—and the uppermost portion of the medulla of one of the sections from the series from which the model was made, which is shown in Fig. 20. The plane of the section is nearly at right angles to the model as placed on the page. The Malpighian corpuscles and tubules belonging to this uriniferous tubule are sketched more deeply than other parts of the figure. The section passes through about the center of the Malpighian corpuscle and through the upper end of the ascending limb, which may be observed as in close proximity to the corpuscle. Of the five cross sections of tubules arranged nearly in a row above the Malpighian corpuscle the first two and the last two are sections of the distal convoluted portion, the middle one and the three nearly longitudinal sections of tubular segments are of the proximal convoluted portions, the lowest one just to the left of the end of the ascending limb marks the end of the proximal convoluted portion, beyond which the tubule becomes smaller to form the descending limb. No part of the loop of Henle nor of the junctional tubule is shown in this section. I have purposely selected for figures sections of these two uriniferous tubules, since they represent tubules of very different form; the arrangement of the sections of the tubules and their relation to the surrounding tubules are therefore very different. These figures may serve to show graphically the difficulties met with in attempting to predict what particular portions of any given section through the cortex of the kidney belong to one uriniferous tubule; a question to which I shall return later.


Fig. 21. A portion of the cortex of two sections of the kidney, from the series from which tubule B, of Fig. 19, was reconstructed. The portions of the tubule represented in these sections are sketched more deeply than the other parts. x 100. For fuller description, see text.


Fig. 22. A portion of the cortex and uppermost part of the medulla fronr one of the series of sections from which the model shown in Fig. 20 was made. xX 100. The parts of this tubule represented in this section are sketched darker than the other parts. For fuller description, see text.


From what has been said concerning the various stages of development of the uriniferous tubules, it may be seen that from a relatively early period in their development—from a stage in which the various parts of the tubules may be considered as differentiated to the extent that the parts are clearly recognized—the different portions of a uriniferous tubule present certain definite relations which ard not materially altered as development proceeds and are maintained in full development. In the feetal as also in the post-foetal kidney the proximal and distal convoluted portions belonging to a uriniferous tubule form a coil complex which shows certain relations to the Malpighian corpuscles of such a tubule, likewise the beginning and ending of the loop of Henle. The coil complex formed by the proximal and distal convoluted portions of a uriniferous tubule is generally situated just above its Malpighian corpuscle, forming a more or less compact mass of convolutions, the main coils of the proximal convoluted portion lying to the inner side—toward the collecting tubule in which the uriniferous tubule terminates—the coils of the distal convoluted portion lying more to the outer side—laterally—although often partly embedded in the coils of the proximal convoluted portion or nearly completely surrounded by them. The proximal convoluted portion leaves the Malpighian corpuscle on its inner side and passes first upwards—toward the periphery of the kidney, as was also shown by Golgi—then forms coils in various directions, ultimately to return to the neighborhood of the Malpighian corpuscle and to pass toward the medulla. The main coils of the distal convoluted portion are usually found a little above the Malpighian corpuscle, one coil or loop generally resting upon it. The upper end of the distal arm of the loop of Henle remains from the time when it may be first recognized in close relation to the Malpighian corpuscle, either passing over it at a variable distance from the origin of the proximal convoluted portion or crossing this near the corpuscle. Hamburger, who has also observed this close relation of the ascending limb to the corpuscle, states that in a number of his. preparations showing various stages of development, he found the upper end of the ascending limb of the loop of Henle in close relation with the Malpighian corpuscle and in the region where the vessels enter and leave it. This, he states, is readily explained when it is remembered that the loop of Henle is originally in the bowl of the “ pseudoglomerulus,” therefore in contact with the developing glomerulus; and as the loop grows in a central direction, the Malpighian corpuscle is fastened to this region by means of capillaries from the vas efferens. Golgi is quoted as saying (Stoerk) that it is the thin arm of the loop which is fastened to the corpuscle in the region of vessel exit. I agree with Stoerk in saying that neither the proximal nor distal arm shows any definite relation to the vessel porta of Bowman’s capsule. That, however, especially the ascending limb of the loop returns for each tubule to the coil complex formed by proximal and distal convoluted portions into the immediate vicinity of its Malpighian corpuscle is clearly shown by all my reconstructions as well as those of Stoerk, as also the tubules obtained by maceration by Golgi and Hamburger, retaining thus in later stages of development and in post-foetal life the relations shown in early stages of development. I have not satisfied myself that the relations become fixed through the agency of arterioles or capillaries, branches of the vas efferens, nor by an especial development of interstitial tissue in this region, although the latter factor seems now and then to play a réle. The descending limb of Henle’s loop in the region where it leaves the coil complex is generally in close relation with the upper end of the ascending limb, sometimes lying to the inner side of it, again over it, therefore also near the Malpighian corpuscle, showing in this respect also in later stages of development the relations borne in early stages of its evolution. The two limbs of Henle’s loop are generally quite parallel and take quite a direct course toward the apex of the Malpighian pyramid. Certain of the loops—those belonging to the tubules which are first developed— extend to near the pelvic epithelium, the apex of the pyramid, retaining in this respect the relations shown in early stages of development, elongating as the medulla develops. Tubules of the several generations which develop later terminate at various levels in the medulla and, in general terms it may be stated, higher up in the medulla for each successive generation of tubules, the loop of those latest formed extending only to the boundary zone of the medulla and even for the adult human kidney, remaining entirely within the medullary rays of the cortex. The descending limb of the loop is the thinner of the two and is lined by a clear, flattened epithelium; the ascending limb, showing the greater diameter, is lined by a cubic epithelium with striated protoplasm; the transition from the thin to the thicker portions of the loop occurs in the tubules reconstructed, at the lower end of the descending limb, at a variable distance from the loop itself, though generally near it. This portion of the descending limb and the loop itself show the same diameter and epithelium as the ascending limb. Schweiger-Seidel found the transition from the thin to the thicker epithelium in about an equal portion of the tubules—1, at the lower end of the descending limb; 2, in the loop itself; 3, at a variable distance from the loop in the ascending limb. His observations have received very general acceptance. Von Ebner, one of the more recent writers, who has slightly modified Schweiger-Seidel’s diagram, states that “the place of thickening is inconstant; now it lies in the descending limb, now in the loop itself, often and quite regularly for loops which extend deep into the pyramid, in the ascending limb.” Hamburger finds for the mouse that the loop itself and the ascending limb are lined by a granular epithelium to a few days before birth; as, however, the leop grows in length with the increase in length of the papilla, the elongation of the loop is obtained through a growth in length of the descending limb, lined by the flattened epithelium, so that the loop is formed by it, and only in the basal portion of the pyramid in the boundary zone are there found loops with the dark epithelium. In making the statement, based on observations made on my models, that the transition from the thinner to the thicker part of the loop of Henle occurs at the lower end of the descending limb, I do so with some reservation, since the models carry the development of the tubules only to the time of birth. I am aware that such statement is open to the criticism that I have applied to Stoerk’s observations relating to the size and structure of the descending limb, namely, that they were made on tubules not fully developed. Yet I have observed a number of loops in series of sections of kidneys from half-grown and full-grown cats and rabbits, situated near the apex of the Malpighian pyramid, the epithelial lining of which consisted of cubic cells with granular protoplasm, while I have not found clear evidence of a loop lined with flattened epithelium. Complete reconstructions of a number of uriniferous tubules from the kidneys of adult animals are necessary to give conclusive answer to this question. My own observations, based on reconstructions, are therefore a confirmation of Piersol’s, who states, “that the relative length of the narrow part of the loop—‘ descending limb ’—and the broader portion vary considerably, but that almost without exception the transition from the conspicuously narrow tube, lined with the peculiar spindle epithelial cells, takes place in the descending limb, often at a considerable distance before the loop itself is reached, so that both limbs in the vicinity of the loop itself are of the same diameter and lined with the same kind of epithelium.”


The junctional tubule, the continuation of the distal convoluted portion, after leaving the coil complex, may pass as a relatively straight tubule or one showing a number of irregularities, for a shorter or greater distance through the cortex, ultimately arching toward the collecting tubule. The concave side of such an arch is turned toward the coil complex formed by the proximal and distal convoluted portions, this lying in fact between the junctional tubule and the collecting tubule to which a given uriniferous tubule is attached. This has also been observed by Stoerk.


In giving thus an outline of the course and the relations shown by the different parts of uriniferous tubules, it should be understood that this can be given only in a general way. For as concerns the form and relations of the proximal and distal convoluted portions and their relation to the Malpighian corpuscle and its relation to the descending and ascending limbs of Henle’s loop, each tubule presents certain slight differences and variations. This the models reproduced will show. No two of the tubules reconstructed are exactly alike or even very nearly so. The several parts of the various tubules present certain characteristic relations, which, though varying more or less, are still to be recognized. The relation of the entire uriniferous tubule to the collecting tubule to which each is attached also varies, and this is quite naturally more true when considering tubules showing later stages of development. In the earlier stages of development, as may have been seen from the figures given of these, the proximal convoluted tubule leaves the Malpighian corpuscle from its inner side and passes behind the upper end of the loop of Henle and, after forming several curvatures, comes forward between the: collecting tubule and the coil complex to reach again the neighborhood of the Malpighian corpuscle and to pass toward the medulla. The loop of Henle, as it leaves the coil complex, is thus in front of the Malpighian corpuscle or the first part of the proximal convoluted portion. As the proximal and distal convoluted portions elongate and form more coils, the whole tubule is often turned on its axis to a greater or less extent, so as to bring the upper end of the loop of Henle more to the inner side of the tubule, nearer to the collecting tubule to which it is attached—in closer relation to the medullary rays. This brings the Malpighian corpuscle from a lateral to a more anterior position and the first part of the convoluted portion from a posterior to a more lateral position. This is shown by a number of models presenting the later stages of development.


Stoerk has called attention to the fact that the Malpighian corpuscles and uriniferous tubules are generally described as presenting in cross sections a round form. This, he states, is, however, not true (at least for fcetal life), as his models show that they present many irregularities. This is to a certain extent true. The Malpighian corpuscles are rarely of exactly spherical form, but show here and there more or less marked depressions and elevations, or they may present a distinctly oval form. The proximal convoluted portion, especially of older stages, is often of a quite regular cylindrical form, now and then for a distance somewhat flattened, but presents as a rule throughout a quite uniform thickness. The tubule of the distal convoluted portion presents often quite marked irregularities of diameter, segments of relatively large diameter being separated by such as show a much smaller diameter; as the tubule presents now and again a sharp bend at one or the other region showing a relatively small diameter, this portion of the tubule may present a quite irregular form. Stoerk has also described and figured small cecal appendages attached to the distal convoluted portion ; these I have not observed in my reconstructions.


In giving the position of the different parts of the uriniferous tubule in the kidney substance, it is generally stated that the proximal and distal convoluted portions, with the Malpighian, corpuscle, are situated in the cortex between the medullary rays, forming the greater part of the cortex. This is confirmed by reconstructions. Further that the distal end of the proximal convoluted portion—the end segment of Argutinsky—enters a medullary ray and with a portion of the descending limb of the loop remains in the ray until the medulla is reached. This is true only for certain tubules, for those the Malpighian corpuscles of which are situated in the cortex above the lowermost two or three tiers of corpuscles, that is, for tubules which present a distinct end segment. The descending limb of the tubules, the corpuscles of which are situated in the lowermost two or three tiers which present indistinct end segments, passes almost directly into the medulla and cannot be said to enter a medullary ray. The loops of Henle for the greater part are found in the medulla, some, as stated, barely reaching the boundary zone, others (the proportions I am not able to give) remaining entirely within the medullary rays. What has been said of the upper end of the descending limb of the loop of Henle applies also to the upper end of the ascending limb. The junctional tubule passes through the cortex between the rays until it arches over to reach the collecting tubule in which it terminates.


I have in connection with Figs. 21 and 22 spoken of the relations, as seen in sections, shown by the coil complex and the Malpighian corpuscles of any given tubule. A study of the sections from which the models were made has not enabled me to formulate any general law concerning this relation. This depends, as may readily be seen, even in what may be regarded as very favorable sections, entirely on the direction of the sections. Frequently the greater part of the coil complex formed by the proximal and distal convoluted portions of a given tubule may be cut in a series of sections without cutting the Malpighian corpuscle of said tubule. The relations of coils of juxtaposed tubules is such that one or more of the loops, especially of the proximal convoluted portion of one tubule, may penetrate for a longer or shorter distance into the coil complex of another tubule, so that in sections the former might readily be interpreted as belonging to the latter. Stoerk gives in Fig. 18 of his article a portion of a section of a kidney showing nephritis hemorrhagica, certain tubules of which contained red blood corpuscles ; this enabled him to select the sections of Malpighian corpuscle and tubules belonging to one uriniferous tubule. The section reproduced shows a characteristic relation of corpuscles and tubules cut, such as is, however, not frequently met with, if I may judge from the sections from which my reconstructions were made. The relations there shown are more nearly approached in Fig. 22 and also in the sections from which model A of Fig. 19 was made than in other series of sections used in modelling the other older developmental stages presented.


It is somewhat hazardous to attempt an estimate of the length of a fully developed uriniferous tubule, without the possession of models showing them in full development. Since, however, the proximal and distal convoluted portions of certain uriniferous tubules attain approximately their full development before the birth of the embryo (cat and rabbit), and since the length of the loop of Henle of these tubules depends on the width of the medulla, as they extend through or nearly through the medulla, an estimate of the length of a fully developed tubule seems justifiable. The length of tubules must necessarily vary, since the loop of Henle, which for the majority of tubules forms their greatest part, must vary in length, since they terminate at different levels in the medulla. An approximation of the length of uriniferous tubules may, therefore, be most readily made for those tubules the Malpighian corpuscles of which are situated in the deepest portion of the cortex, the loops of Henle terminate presumably near the apex of the Malpighian pyramid. The most fully developed tubule, showing a typical arrangement of parts, that I have reconstructed, is the one shown in Fig. 20. This is from the kidney of a cat embryo, obtained a few days before birth, and measures 9 mm. In one of the sections of this kidney containing nearly the entire length of the distal limb of the loop of Henle of this tubule, the width of the medulla is approximately 2.22 mm. (the junction of the cortex and medulla does not form a straight line), very nearly one-half the entire length of the loop of Henle (4.85 mm.). In sections passing through the middle of the Malpighian pyramid of the kidney of a full-grown cat, the medulla has a width of approximately 12 mm. Assuming, therefore, that the loops of Henle of certain of the uriniferous tubules of this kidney, the Malpighian corpuscles of which are situated in the deepest portion of the cortex, traverse the entire width of the medulla, and one is justified in doing this, since loops are seen in section near the very apex of the pyramid; such a loop would have a length of approximately 24 mm.; add to this the length of the proximal convoluted portion, which may be given at 2.5 to 3 mm., the distal convoluted portion about 1 mm., and the junctional tubule about 2mm. (the width of the cortex in the sections from which the measurements for the medulla were given varies from 2.5 mm. to 3 mm.), the entire length of such a uriniferous tubule would be approximately 3 cm. Other tubules, the loops of Henle of which do not pass so deep down in the medulla, would show a correspondingly shorter length, the shortest ones measuring, if I may be allowed to estimate, 10 mm. to.12 mm.


V. Ebner quotes Schweiger-Seidel as stating that the proximal convoluted portion of a uriniferous tubule forms about one-fourth to onefifth of the entire uriniferous tubule, while the distal convoluted portion, which is shorter than the proximal portion, is about one-seventh of the latter’s length. As concerns the relative length of the proximal convoluted portion, this may be regarded as correct for tubules with relatively short loops of Henle. In tubules with relatively long loops of Henle it forms a relatively shorter portion—from one-eighth to onetenth of the entire tubule. So far as I am able to judge from my own models and from other observations, the distal convoluted portion presents a length which is about one-third to one-fourth that of the proximal convoluted portion. If other estimates of the length of uriniferous tubules or of parts thereof are to be found in the literature, they have escaped my notice.


It is not my purpose to enter here on a discussion of the epithelium lining the different parts of a uriniferous tubule. For this the reader is referred to Disse’s quite recent account, he himself having made noteworthy contributions to this point. The observations made on the sections from which the models were made lead me to recognize three distinct varieties of epithelium in a uriniferous tubule:

  1. The epithelium lining the entire proximal convoluted portion, to the region in the upper part of the descending limb, where the tubule is quite rapidly reduced in size, where it assumes the shape and structure of the narrow portion of the limb. The epithelium of the proximal convoluted portion is sufficiently known to obviate an especial description of it.
  2. The clear, flattened epithelium of the descending limb of the loop in the region in which it presents a small diameter. I have gained the impression that too much emphasis is put on the statement that the cells of this epithelium are thicker in the region of the nucleus, thus bulging into the lumen of the tubule, and as the nuclei do not lie opposite, but alternate in the course of the tubule, its lumen is not of the cylindrical form, but irregular—wavy as seen in sections. In sections from material which I have regarded as showing good fixation, the lumen of this portion of the uriniferous tubule presents a much more regular outline than in sections from material not so well fixed, the cells presenting throughout a more uniform thickness. The suggestion is therefore made that the description, as generally given, refers to preparations which do not present the correct structure of this portion of the uriniferous tubules. This point is reserved for further investigation.
  3. The last portion of the descending limb, the loop itself, the ascending limb, the distal convoluted portion, and the junctional tubule to near the collecting tube present an epithelium which shows great similarity of form as well as structure. The lining cells show a form which is irregularly cubical or short columnar. Disse describes the epithelium of the ascending limb as showing indistinct cell boundaries, while these are more distinct in the epithelium of the distal convoluted portion ; the protoplasm of the latter, although granular, is also described as being clearer. In both regions the cells show an outer dark zone which is finely striated and an inner zone which is lighter, the nuclei being placed at the junction of the two zones. In my own preparations the epithelium lining the ascending limb and the distal convoluted portion do not respectively present a structure which differs to a degree making it necessary to group them separately, and I have, therefore, placed them under one head. The uriniferous tubule, for a short though variable distance, before reaching the collecting tubule, presents an epithelium which is like that of the small collecting tubules. This short segment may be spoken of as belonging to the collecting tubule or with equal propriety as forming part of the uriniferous tubule proper, as it is difficult to state with any degree of certainty whether it develops as an outgrowth of the collecting tubule or is differentiated with the other parts of the uriniferous tubule from the renal vesicle.


Fig. 23 Oiagrams Showing The Different Conceptions Held Of The Form Of The Uriniferous Tubule.

A, Schweiger. Seidel's diagram (aa given by Stoerk, 1904, Fig. Ja); B, Von Ebner's diagram (K6lliker’s Handbuch d. Gewebelehre des Menschen, Erste Halfte, I1f, Bd.. Fig. 1002); C. Haycraft’s diagram of a uriniferous tubule of a rabbit, Fig. 13; D, Golgi's figure (Stoerk, 100, Fig. 21'; E. Diase’s diagram (Bardeleben's Handbuch d. Anat. des Menschen, Harn und Geschlechteorgane, Erster Theil, VIL Bd., Fig. 16); F, Stoerk’s diagram (1904, Fig. 27).


Before giving by way of a diagram or scheme the shape of a uriniferous tubule and its relation to a collecting tubule, as this presents itself to me, brief mention may yet be made of a number of diagrams of uriniferous tubules found in the literature, each of which presents certain characteristics which make it different from the others selected. These I have grouped under Fig. 23. The different conceptions of the form of a uriniferous tubule held by the authorities presenting the diagrams here given and their departure from the conception of the form of a uriniferous tubule as presented in Fig. 24 may be most readily expressed in this graphical manner.


In A, Schweiger-Seidel’s diagram, is given inaccurately the relative position of the Malpighian corpuscle and proximal and distal convoluted portions, more especially the distal convoluted portion which is separated too much from the proximal convoluted portion. In B, Von Ebner’s diagram, an attempt is made to bring the distal convoluted portion in relation with the Malpighian corpuscle (accepting Hamburger’s observations) and to show that the first part of the proximal convoluted portion extends toward the cortex (Golgi). The diagram presents inaccuracies in the relations given to the Malpighian corpuscle and the proximal and distal convoluted portions. In C, Haycraft’s diagram, of a uriniferous tubule of a rabbit, he presents, as is obvious, deductions drawn from the study of a tubule showing an early stage of development, shown in his Fig. 10. This, as I have stated, very probably presents parts of two tubules, there sketched as one. His diagram is wrong in the position given to the Malpighian corpuscle and as to the length, shape, and relative position of the proximal and distal convoluted portions. D, one of Golgi’s figures, shows a uriniferous tubule at a relatively early stage of development. This is not a diagram, but the figure is introduced, since it shows quite correctly the relations of the different parts of a uriniferous tubule. #, Disse’s diagram, one of the most recent at hand, gives incorrectly the relations shown by the ascending and descending limbs of Henle’s loop to the Malpighian corpuscle and the course of the first part of the proximal convoluted portion. F', Stoerk’s diagram, based on reconstructions of uriniferous tubules, presents a number of inaccuracies, as is shown by my own observations on models of uriniferous tubules showing much older stages of development than the oldest tubule reconstructed by him. In this diagram, the Malpighian corpuscle is relatively too large, the course given to the first part of the proximal convoluted portion is too regular; the proximal convoluted portion is relatively too short when compared with the length given to the distal convoluted portion, but especially wrong is the diagram in the presentation given of the descending limb of Henle’s loop. This, as given by Stoerk, shows essentially the same diameter as the proximal convoluted portion (in his description he gives it a similar epithelial lining), disregarding entirely that portion of the descending limb of the loop which shows a flattened epithelium.




Fig. 24. Diagram of three uriniferous tubules and their relation to a collecting tubule; A, of a tubule, the Malpighian corpuscle of which is situated in the lowermost portion of the cortex; B, about the middle of the cortex; C, in the outer portion of the cortex. m, Malpighian corpuscle; v, vessel porta; n, neck; pc, proximal convoluted portion; es, end segment; di, descending limb, al, ascending limb of the loop of Henle; dc, distal convoluted portion;. j, junctional tubule; c, collecting tubule (Huber).


In the diagram of Fig. 24 the loop itself of the loop of Henle is given as formed by a tubule the same as that of the ascending limb, the transition from the thinner to the thicker portion of the limb as occurring in the lowermost part of the descending limb. This is in conformity with my models. In discussing this point, I have stated that this observation was given with some reservation. I have, therefore, not called especial attention to certain of the loops shown in the diagram A, B, and F of Fig. 23, which are formed by the thinner portions of this structure.


In conclusion, I desire to thank Julius H. Powers and Edward G. Huber for assistance given me in the reconstructions, and Elton P. Billings and Frederic G. Johnson for assistance rendered in making the illustrations,—students of medicine in the Department of Medicine of the University of Michigan.


Literature Cited

Contributions not seen in the original are marked with an asterisk (@).

Batrovur, F. M. — On the Origin and History of the Urinogenital Organs of Vertebrates. Jour. Anat. and Phys., Lond., Vol. X, 1876.

@ BornuHavupt, TH. — Zur Entwickelung des Urogenitalsystems beim Htihnchen. Inaug. Diss., Dorpat, 1867.

Braun, M. — Das Urogenitalsystem der einheimischen Reptilien, entwickelungsgeschichtlich und anatomisch bearbeitet. Arbeiten a. d. zool.zoot. Inst., Wiirzburg, Bd. IV, 1878.

Cutevitz, J. H. — Beobachtungen und Bemerkungen iiber Sdugethiernieren. Arch. Anat. u. Phys. Supplement Band, 1897.

Cotsere, A. — Zur Anatomie der Niere. Centralb. med. Wissenschaft., Vol. I, 1863.

Dissz, J — Harn und Geschliechtsorgane. V. Bardeleben’s Handbuch der Anatomie des Menschen, Bd. VII, Erster Teil, Jena, 1902.

v. EBNER, V. — Kolliker’s Handbuch der Gewebelehre des Menschen. Bad. III, 1 Halfte, Leipzig, 1899.

Emery, C. — Recherches embryologiques sur le rein des mammiféres. Arch. ital. Biol., Tome IV, 1883.


FELix. — Entwickelung der Nachniere. Hertwig’s Handbuch der vergleichenden und experimentellen Entwickelungslehre der Wirbelthiere, Page 302, Part 20, 1904. (Not yet completed.)

FURBRINGER, M. — Zur vergleichenden Anatomie und Entwickelungsgeschichte der Excretionsorgane der Vertebraten. Morphol. Jahrb., Bd. IV, 1878.

GERHARDT, V. — Zur Entwickelung der bleibenden Niere. Arch. mikr. Anat. LVII, 1901.

@ Golgi, C. — Annotazioni intorno all’ istologia dei Reni dell’ Uomo e di altriMammiferi. Rendiconti delle R. Accad. dei Lincei, Vol. V, Serie I, 1889.

Gregory, E. R. — Observations on the Development of the Excretory System in Turtles. Zool. Jahrbiicher Abth. f. Anat. u. Ontog. d. Thiere, Bd. XIII, 1900.

HAMBURGER, O. — Ueber die Entwickelung der Saugethierniere. Arch. Anat. u. Phys. Supplement, Bd. 1890.

Haveu, E. — Ueber die Anatomie und Entwickelung der Niere. Anat. Hefte, Bd. XXII, 1903.

Haycraft, J. B — The Development of the Kidney in the Rabbit. Internat. Monatsschr. Anat. u. Phys., Bd. XII, 1895.

Herring, P. T. — The Development of the Malpighian Bodies of the Kidney and its Relation to the Pathological Changes which Occur in them. Journ. Path. and Bact., Vol. VI, 1900. HILDEBRAND.—Weitere Beitrage zur pathologischen Anatomie der Nierengeschwiilste. Arch. f. klinische Chirurgie, Vol. XLVIII, 1894. HoFFMANN, C. K.—Zur Entwickelungsgeschichte der Urogenitalorgane bei den Reptilien. Zeitschr. f. wissensch. Zool., Bd. XLVIII, 1889.

HortoLris, Cu. — Recherches histologiques sur le glomérule et les épithéliums du rein. Arch. de physiol. normale et pathol., 1881.

JANOSIK, J. — Histologisch-embryologische Untersuchungen iiber das Urogenitalsystem. Sitz. Ber. Akad. Wiss. Wien., math.-nat. K1., Bd. XCI, III Abth., 1885.

@ Kallay, A. — Die Niere im friihen Stadium des Embryonallebens. Mitth. a. d. embryol. Inst. d. K. K. Univ. in Wien, Neue Folge, Heft I, 1885.

KEIBEL, F. — Ueber Entwickelung des Urogenitalapparates von Echidna. Anat. Anz, Erginzungsheft, Vol. XXIII, 1903.

KoLLIKER, V. — Entwickelungsgeschichte des Menschen und der héheren Thiere. Leipzig, 1879.

KoLlmann, J. — Lehrbuch der Entwickelungsgeschichte des Menschen. Jena, 1898.

Kuprrer, C. — Untersuchungen tiber die Entwickelung des Harn- und Geschlechtssystems. Arch. mikr. Anat., Bd. I, 1865.

Liwe, L. — Zur Entwickelungsgeschichte der S&ugethierniere. Arch. mikr. Anat., Bd. XVI, 1879.

MEYER, Ericu. — Ueber einige Entwickelungshemmungen der Niere. Miinchen. med. Wochenschr., May, 1903.

Minot CS. Human Embryology. (1897) London: The Macmillan Company.

Nacet, W. — Ueber die Entwickelung des Urogenitalsystems des Menschen. Arch. mikr. Anat., Bd. XXXIV, 1889.

PrersoL, G. A. — Note on Henle’s Loops of the kidney. University Medical Magazine, March, 1889.

Pyr, W. — Observations on the Development and Structure of the Kidney. Journ. Anat. and Phys., Lond., Vol. UX, 1875.

@ Remak, R. — Untersuchungen tiber die Entwickelung der Wirbelthiere. Berlin, 1855.

Ribbert, H. — Ueber die Entwickelung der Glomeruli. Arch. mikr. Anat., Bd. XVII, 1880.

Ueber die Entwickelung der bleibenden Niere und iiber die Entstehung der Cystenniere. Verhandl. d. Deut. path. Gesellsch., Berlin, 1900.

Riede, K. — Untersuchungen zur Entwickelung der bleibenden Niere. Inaug. Diss. Miinchen, 1887.

@ Riedel. — Entwickelung der S&ugethierniere. Unters. aus dem anat. Inst. zu Rostock, 1874.

Rickert, J. — Entwickelung der Excretionsorgane. Ergebnisse Anat. u. Entwickelungsgesch., Bd. I, 1891.

ScureEinER, K. E. — Ueber die Entwickelung der Amniotenniere. Zeitschr. wissensch. Zool., Bd. LX XI, 1902.

ScHuLrzE, O. — Grundriss der Entwickelungsgeschichte des Menschen und der Saugethiere. Leipzig, 1897.

SrEpGEwick, A. — Development of the Kidney in its Relation to the Wolffian body in the Chick. Quart. Journ. mikr. Sc., Vol. XX, New Series, 1880,

Stoerk, O. — Ueber Nierenverinderung bei Lues congenita. Wiener klin. Wochenschr., XIV Jahrg., 1901.

Beitrag zur Kenntniss des Aufbaus der menschlichen Niere. Anat. Hefte, Bd. XXIII, Heft 2, 1904.

SrrauL. — Entwickelungsgeschichte und Missbildungen der Nieren, in Kiister, Chirurgische Krankheiten der Nieren. Lieferung 52 B, Stuttgart, 1902,

THaysseN, A. — Die Entwickelung der Niere. Vorlaéufige mittheilung. Centraibl. f. med. Wissénsch., Bd. XI, 1873.

ToLtpt, C. — Untersuchufgen tiber das Wachsthum der Nieren des Menschen und der S&ugethiere. Sitz. Ber. Akad. Wiss. Wien, math.-nat. KI]. Bd. LXIX, III Abth., 1874.

WALDEYER, W. — Hierstock und Hi. Leipzig, 1870.

WEBER, S. — Zur Entwickelungsgeschichte des Uropoetischen Apparatus bei Sdugern, mit besonderer Beriicksichtigung der Urniere zur Zeit des Auftretens der bleibenden Niere. Morphol. Arb., Bd. VII, 1897.

WIEDERSHEIM, R. — Ueber die Entwickelung des Urogenitalapparatus bei Cro codilen und Schildkréten. Arch. mikr. Anat., Bd. XXXVI, 1890.



Cite this page: Hill, M.A. (2020, October 28) Embryology Paper - On the development and shape of uriniferous tubules of certain of the higher mammals (1905). Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Paper_-_On_the_development_and_shape_of_uriniferous_tubules_of_certain_of_the_higher_mammals_(1905)

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