Paper - Anomalies of the genito-urinary tract

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Abbott 1930 Anomalies of the genito-urinary tract. (1930) J. Can. Med. Assoc. -226.

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This historic 1930 paper by Abbott describes the abnormalities in the development of the human genital and renal systems.



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Anomalies of the Genito-urinary Tract

by A.C. Abbott, B.A., M.D., c.M., F.R.C.S. (EDIN.),

Winnipeg

Introduction

The knowledge of urology has advanced at such a rapid rate in the past twenty years that it is now possible to make more exact diagnosis in this field than in any other branch of medicine and surgery.

One of the first essentials in urological surgery is a thorough knowledge of the embryology of the genito-urinary tract. This knowledge impresses one with the fact that to separate the organs of excretion from those of reproduction is a difficult matter, so intimately are they associated, both anatomically and embryologically. So clearly is this recognized that to-day many practitioners are found combining work in gynaecology and urology.


Fig. 1. Cross section of an embryo about the 4th week, showing position of the intermediate cell mass. (Cabot).


Anomalies of the genito-urinary tract are not uncommon. In routine cystoscopic work, one finds a number of them. Polycystic kidneys are moderately common and a number of solitary cysts have now been reported. Probably the commonest anomaly is the accessory renal artery or vein. This condition is most important from a surgical point of view, as an accessory artery can be very troublesome, and in some cases a fatal issue has resulted when it has been torn when *a kidney was being delivered.

Embryological Considerations

A short Summary of the embryology of the genito-urinary system is necessary to properly illustrate the cases which I wish to present.


Fig. 1 shows a cross section of an embryo about the fourth week of embryonic -life. Situated between the lateral plates of mesoderm and the primitive segments is a mass of cells called the intermediate cell mass. This extends throughout the whole length of the embryo and is subdivided transversely into segments or somites. The. somitesare few at first, but as the embryo develops they increase in number. It is from this group of cells that the greater part of the genito-urinary apparatus is developed.


Fig. 2. Diagrammatic section through pronephric structures; Wd, Wolflian duct; N, nephrostome; Coe, coelom; Eg, external glomerulus.


In the development of the urinary apparatus there is a succession of three kidney organs. The first to make its appearance is the “pronephros,” in the third week when there are only nine or ten pairs of somites. It has its begin ning as a series of evaginations from the coelom into the intermediate cell ma-ss dorsally. These evaginations form a series of transverse tubules, each of which communicates with the body cavity by a ciliated funnel-shaped op-ening as will be seen in fig. 2. In the course of each duct a glomerulus is formed. The dorsal end of each tube turns toward the tail of the organism and unites with a similar duct in the segment posterior to it. In this way a longitudinal tube is formed which is called the primitive excretory duct. This duct grows caudally, and in its later development joins with the cloaca. This mass of tubules is called the pronephros, and while its cephalic end is degenerating its caudal end is developing. Its life history is very short, extending approximately over the fourth week of embryonic life, and it then becomes vestigial. We might pause here to point out that all the transverse tubules and glomeruli atrophy completely. The primitive excretory duct remains and serves as the duct for the second kidney organ, the mesonephros.


Fig. 3. Development of the mesonephros. (Arcy).


While the pronephros is undergoing its development and its degeneration, caudally, extending through the lower cervical, the dorsal and the upper lumbar segments, the mesonephros or second kidney organ is developing. It makes its appearance as a series of solid rods of cells running dorsally and laterally in the intermediatecell mas-s. These little rods of cells become canaliculized and join with the primary excretory duet of the pronephros. This is best illustrated by fig. 3. Medially, the closed


end of the duct becomes pushed in or invaginated by a tuft of blood vessels forming a glomerulus. It will be remembered that in the pronephros there was but one tubule to a somite. In the mesonephros there are many, and in this organ also, which actually functions, one finds the cephalic tubules degenerating while those caudally are forming. The little rod of cells which became canaliculized has gradually become tortuous and its medial end bulbous so that a glomerulus may be formed. Laterally and posteriorly they join the primitive excretory duct. Altogether, about eighty-three pairs of tubules are formed, beginning in embryos of 2.5 mm. By the time the embryo has reached the length of 21 mm. only twenty-five approximately remain. The secreting portions of these twenty-five tubules degenerate, leaving two groups of the collecting portions, the anterior, cephalic or epigenitalis, and a small posterior group.


Fig. 4. Drawing showing division of the primitive cloaca into the urogenital sinus anteriorly and the rectum posteriorly. It also shows the budding of the ureter from the lower end of Wolflian duct. (Young).


I might here point out that the sex gland has been developed in this cephalic region. It unites with the epigenitalis at about the 60 mm. stage. The union takes place at the rete testis, a.nd the collecting tubules of the epigenitalis become the efferent ducts. They empty into the Wolffian duct, the proximal end of this duct later becoming the cpididymis and the distal portion the vas deferens and the ejaculatory duet. It will therefore be seen that this little embryonic organ is of great importance in the development of the male sex organs. In the female, however, it is different. Union takes place at the rete ovarii. Here the epigenitalis with a portion of the Wolffian duct becomes cut off and remains as the epoiiphoron while the remnant of the distal portion of the mesonephros forms Gartner’s duct. The caudal portion of this embryonic structure is not so important, giving rise to the paradidymis in the male and the par-oophoron in the female.

We come now to the formation of the permanent kidney which has been developing simultaneously with the pronephros and the mesonephros.

The true kidney has a double origin. The secreting portion, including Bowman’s capsule with the glomerulus, the ascending and descending‘ loops of Henle, and the convoluted tubules, arise from a condensation of a group of cells in the nephrogenic fold at this level. The collecting tubules, calyces, pelvis and ureter arise from the outgrowth from the lower end of the Wolffian duct.


Fig. 4 shows that the rectum and urogenital sinus are being separated by a mass of tissue pushing‘ caudally into the primitive cloaca. The Wolffian duct normally retains its connection with the urogenital sinus as is shown in this drawing. From the lower end of this duct a little evagination takes place, which grows posteriorly as aureteral bud (U.B.) and is the embryonic beginning of the collecting portion of the kidney. It grows dorsally but shortly turns upwards; it grows in length; its distal end expands and becomes divided into two primary collecting tubules, one lying cephalically and one caudally. Usually two others appear between these. From the ampullary swelling at the end of each primary tubule, two to four secondary ‘tubules sprout. These in turn divide and re-divide until we have about twelve generations. The primary tubules go to form the major calyces, the secondary ones the minor calyces. Three and four are absorbed into the second, so that the fifth order, twenty or thirty in number, open into the second. The remaining orders of tubules constitute the collecting tubules which form the greatest part of the medulla of the adult kidney.


When the primary tubules were formed the nephrogenic cap about the primitive pelvis subdivides, and as each succeeding order is formed it again divides, and so on, always leaving the terminal branch of the tubule with its cap of nephrogenic tissue. The converging branches of such a tubular tree constitute the primary renal unit or pyramid. The nephrogenic tissue forms the cortex of the kidney and each subdivision covering the tubules of the pyramid peripherally is marked on the surface by a depression. The fetal kidney is thus distinctly lobed and this lobulation persists for many years. The nephrogenic tissue dips down to the pelvis between the pyramids, forming Bertini’s columns.

fiG. 5.—Progressive development of the secreting portion of the permanent kidney. (Arcy).

Having traced the formation of the, collecting portion of the urinary system, we must now look at the development of the secreting portion around each terminal end of the collection tubule. The nephrogenic tissue becomes condensed into small, solid, spherical masses, one for each tubule (See fig. 5). Each sphere is converted into a vesicle with eccentrically placed lumen. This vesicle elongates and becomes “S” shaped, its outer wall uniting with a collecting tubule and its inner thinner wall forming Bowman ’s capsule. It now grows in length forming a proximal convoluted portion, Henle’s loop, and a distal‘ convoluted tubule. Arteries from the surrounding tissue push their way into Bowman’s capsule and a glomerulus is formed, which is fully developed at the end of the second month.‘ It is convenient to stop at this point and show some of the common errors that we find in the embryological development of the kidney. It is possibly best to begin with the kidney, and we turn to: A 220

Congenital Anomalies of the Kidney

1. The polycystic kidney. — In this case the kidney is simply studded with small watery cysts. The most plausible explanation of this was given by Hildebrandt who based his theory on the dualistic origin of the kidney tubules. If it is recalled how the secreting and collecting tubules of the permanent kidney were developed separately it is possible to theorize on what might happen. Hildebrandt believed that if they do not unite the secreting tubules become cystic. This is possibly the explanation, but one cannot get away from the practical fact that dye injected into the pelvis in some cases finds its way into the cysts.

The diagnosis is suggested by bilateral swellings in the kidney area. The condition is moderately common. Pyelograms are variable and dangerous, and treatment is usually limited to medical therapy.


2. Solitary cysts of the kidney. — Solitary cysts of the kidney are very rare. Up to 1924 only sixty had been reported in the literature.

CASE 1

A case that came under my own observation was that of a woman admitted to the Winnipeg General Hospital under the care of Dr. R. D. Fletcher. She had at first consulted her physician on account of gastric symptoms, chiefly nausea and vomiting, and marked loss of weight. On examination . two salient points were noticed. A bismuth meal showed a large extra-gastric filling defect in the greater curvature of the fundus of the stomach. A large smooth tumour mass was to be felt in the left hypochondrium. Al diagnosis of hypernephroma was made.

The usual oblique incision in the loin was made, and much to our surprise we found a large solitary watery cyst, the size of a small football, on the convexity of -the centre of the kidney. This was removed by dissecting the cyst oif the kidney. The kidney was closed with mattress sutures and dropped back into the cavity from which it was taken. The patient made an uneventful recovery.

The post-operative history of this patient was very interesting. She was well for three months, then all the former symptoms recurred. After two or three years she again had an x-ray taken, and an ulcer was found on the lesser curvature of the stomach. At that time she weighed eighty pounds. She was put to bed on a strict Sippy diet, and now, three years later, has entirely regained her health, weighs 156 pounds, and is once more enjoying life. I think we are therefore justified in saying that the kidney condition was incidental, and that her real trouble was gastric ulcer.

The embryological explanation of solitary cysts is uncertain. Some say they arise from embryonal rests, proliferating from extrinsic causes. Others believe them to be caused by failure of union between the collecting and the ureter.

secreting portions of the tubules. Caulk and Cunningham believe that the condition is due to a sclerosis in the kidney, with extra-canalicular obstruction. None of these theories is proved.

Frequently, one finds vestiges of renal substance in the walls of these cysts. Some are lined with epithelium and some are not. The contents are sometimes clear and sometimes bloody.


We must now pass on to the development of As fig. 4 shows the ureter arises from the lower end of the Wolfiian duct. urogenital sinus now begins to expand and does so partly at the expense of the lower end of the Wolfiian duct. The urorectal septum, pushing its fold of mesoderm in front of it, passes further down, and finally completely separates the rectum and urogenital sinus.


Fig. 6. Deve1opment of complete duplication of kidney. Note how the ureter, which originally arose lowest down from Wolflian duct, comes to lie highest in bladder. (Cabot).


The opening of the ureter into the Wolffian duct becomes widely separated and lies above and lateral to the opening of the Wolfiian duct. This is due to the expansion of the bladder.


We have now reached the stage where we can explain the occurrence of a double ureter. Instead of one ureteral bud arising from the Wolffian duct there are two. This is shown in fig. 6. Here again, the lower end of the Wolffian duct is taken up by the bladder. The lowest ureteric bud is taken up first and carried upwards and outwards on the bladder wall. The upper one follows and is likewise carried upwards and outwards, but never so high or laterally as the first. Therefore, the ureteric orifice which drains the upper portion of the kidney opens lowest on the bladder wall. This is and always must be a constant arrangement. The ureters are thus crossed as shown in this figure. This is what occurs in a complete duplication. Some say it is possible to have two ureteral buds, which later fuse, giving rise to a single ureter above. This is a disputed point in embryology. We commonly find, however, a single ureteral orifice with a single ureter to begin with, and a variable distance from the bladder wall the ureter splits, giving rise to a double ureter up to the kidney. fig. 7 represents variations that Hugh C'abot has actually seen in his own practice.

fiG. 7 .—Various types of ureteral anomalies. (Cabot).

The. table below gives an outline of the anomalies found in the kidney and ureter.

ANOMALIES or Kmnmrs

1. Number

(a) Bilateral absence (b) Unilateral absence (c) Supernumerary, free or fused.

2. Form

(a) Annular-short-long, etc. (b) Fused kidneys:

1. Horseshoe

2. Disk

3. Sigmoid

4. Other variations.

3. Position (8.) Simple dystopia (b) Crossed dystopia. 4. Structure (a) Congenital hypertrophy

(b) ‘ ‘ hypoplasia (c) ‘ ‘ atrophy (d) ‘ ‘ _ cysts:

1. Multiple

2. Solitary.

5. A-nomalous vessels 1 ANOMALIES or URETER

1. Number

2. Position

3. Anomalies of ureteral orifice 4. Anomalies of implantation.

I have seen no case of bilateral absence. These are necessarily incompatible with life. I have had two cases which I have classified as unilateral absence.

CASE 2

The first was a public case at the Winnipeg General Hospital. A cystoscopy showed a normal right ureter on a normal ureteric ridge. On the left side the bladder wall was smooth. There was no ridge and no ureteral orifice. The possibilities in this case might be: (a) complete absence of the kidney; (b) failure only on the part of the ureteric portion;_ (c) it might be that the ureteric orifice was abnormally planted into the rectum,,se_minal vesicle, ejaculatory duct, vagina, etc.

Unfortunately no effort was made to check this up, but the clear plate showed‘ no kidney shadow on the left side. The ureter opening into the rectum could be discovered by injecting indigo carmine intravenously and checking the rectum for the dye.

My second case is a recent one.

CASE 3

This boy at the age of nine or ten was admitted to the Sick Children ’s Hospital in Edinburgh with a pain in the right side. He was thought to have appendicitis and this area was explored. Not enough was found to account for his pain and the incision was extended upwards and downwards. A large hydroureter with nothing on its upper extremity was found and removed. I am presenting this case as an illustration of failure of the secreting portion of the kidney to develop. He now has.pain in the left loin. . The pyelogram shows a -congenital solitary kidney with hypertrophy (see fig. 8). The enormous hypertrophy was verified by palpation. In this case there were two ureters. I

I have met with no supernumerary kidneys. These may be free or fused. As to variations in form, I have seen none except. an occasional congenitally lobulated kidney. Anyone interested in this type of kidney will find practically all

kidneys up to the age of four showing congenital lobulations.


M alpositz'0n.—Simple dystopia is where the kidney is abnormally placed on its correct side. These cases are distinguished from floating kidneysiby the fact that the kidney is usually malformed and that the ureter, being shorter

fiG. 8.—Congenital solitary kidney (author ’s case).

than normal, usually runs a straight course

from the bladder to the kidney. Dr. Donald F. McIntyre has been good enough to allow me to report the next case.

CASE 4

This young woman had a mass in her right iliac fossa. Cystoscopy and pyelogram revealed an abnormal kidney in the right iliac fossa (fig. 9).

You will note three things in this pyelogi-am:—

1. There is no sudden kink in the ureter, the curves being smooth and regular.

2. The calyces point forward and inwards. Therefore, this illustrates non-rotation of the kidney.

3. The kidney lies in the false pelvis and has never been any higher.

The following case history illustrates, in contrast, an acquired ptosis of the kidney.

CAsE 5

This woman had for years typical Diet1’s crises. A pyelogram done with the patient lying flat, showed a marked kink in the upper ureter (fig. 10). One position‘ showed this marked distor taken in the erect t1on'.~‘(F1g. 11). This kidney was suspended sixteen

months ago and the patient has had*,no pain since.

I operated on one such case four years ago with no relief. c

Crossed dystopia is where the ureter opens into the correct side of the bladder, but its kidney lies on the opposite side of the body. Embryologically, this is hard to explain.

I have had no case of congenital atrophy or hypoplasia. Polycystic kidney and solitary cyst of the kidney have already been referred to.

Anomalies of the renal vessels.— Anomalous renal vessels are common. They may arise from

Fig. 9. Simple dystopia and non-rotation. (McIntyre’s case). the aorta, common iliac, internal iliac, middle sacral or inferior mesenteric artery. They are practically always present if there is any ab _ normality of the kidney. Three years ago, Dr. Martin Spooner and I dissected sixteen stillborn babies. Of these, nine had abnormal renal vessels. The following details are of interest in these sixteen cases.

CASE 6

A nine months’ still-born baby boy with two left A renal veins.

CAsE 7

A ten months’ macerated baby; an extra-uterine gestation in the right broad ligament. normal; the left side (a) showed the vein posterior to the artery; (b) the middle suprarenal artery rising from the left renal artery.

Right side was

CAsE 8

A nine months’ baby, still-born. The left kidney was normal; the right had two distinct arteries which arose from the aorta about 2 mm. apart.

CAsE 9

Two accessory renal arteries, of one-third normal size, arose opposite each other from the aorta and passed to the lower pole of the kidney anterior to the ureter.


CASE 10

On the left side an accessory renal artery passed to the lower pole anterior to the ureter.

CASE 11

Accessory renal arteries ran to the lower angle of the hilum on the right and left sides. They were of equal size, equal to the renal artery proper, and entered the hila.

CASE 12

A large branch from the normal left renal artery passed to the upper pole of the kidney.

Fig. 10.—Floating kidney with patient in the horizontal plane (author’s case).

CASE 13

A premature baby who lived eighteen hours. It had a spina bifida involving the lower dorsal and upper lumbar area. The legs were congenitally deformed. They were short, acutely flexed, and held in this position by a fold of skin which extended almost half way down the calf and up the thigh. There was no intestinal anomaly. The right kidney possessed three right renal arteries, an arising from the aorta, all entering the hilum, and two renal veins. The ureter and pelvis were normal. The left kidney had two renal arteries entering the hilum from the aorta and three renal veins which passed posteriorly to the aorta to the hilum. The pelvis and ureter were normal. The foramen ovale was wide open. The ductus arteriosus was present. Here the left renal artery gave off a branch to the upper pole.

CASE 15

Normal, except that there was a congenital valve of the urethra which will be spoken of later.

The explanation of abnormal renal vessels probably lies in the fact that the kidney is

vascularized before its upward migration, and that these vessels, normally lost, are retained. The view that the kidney acquires its blood supply after it reaches its final position is wrong. By that time the aorta is a well-formed vessel with thick mesenchymal walls ; it is quite unable to give off further branches.

Abnormalities of the Ureter

We now come to some (personal) abnormal ureteral cases. I have met with a number of ureteral anomalies, but will only describe four.


Fig. 11. The same case as in fig. 10, butthe patient is in the erect position. Note the rotation and accentuation of kink in ureter (author’s case).

CASE 16

The first is of a young girl with right sided‘ pain and a few blood cells in her urine. Provisional diagnosis —kidney or appendix trouble. The clear plate was negative. A pyelogram showed a duplicate ureter about three inches below the pelvi-ureteral junction. The ureter and pelvis were otherwise normal.

One point in diagnosis. The lower pelvis, as outlined in the pyelogram was not large enough for the kidney shadow. There must be, therefore, another ureter and pelvis draining the upper part of that kidney. A bismuth series showed a painful tender caecum, and a subacute retrocaacal appendix was removed.

The next was a public case at the General Hospital.

CASE 17

The patient complained of chronic pain in the right loin. She was cystoscoped and the right ureter wa catheterized. A pyelogram was made and here again we found a large kidney shadow and a small pelvis in the lower ‘portion. A second cystoscopy revealed another ureter lower down on the ureteric ridge, draining a congenitally small pelvis high up In the kidney (fig. 12).

This is an example of a complete duplication. on the right side. CASE 18

The next case is a woman of forty-nine. She had had severe attacks. of pain in. the left side for twenty years. She was admitted to the hospital with a temperature of 103°, very severe pain and marked tenderness in the left loin and a clear urine. I saw her one Saturday night, and palpation revealed very rigid abdominal muscles and much "pain in her left side. I noted that she had a clear urine. I decided to cystoscope. her in the morning and put in a catheter for drainage as I felt that she had a closed, infected left kidney. In the morning her urine was loaded with pus. Her temperature was normal. Cystoscopy revealed two urethral orifices on the right side. There was one on the left, but in doing a pyelogram we saw two things (fig. 13), a« kidney shadow too large for the pelvis and another ureter partly outlined beginning lower down. This was due to the fact that the sodium iodide refluxed up the branching ureter. I cut down on the left kidney. There were two ureters and two renal arteries. The upper half of the kidney was a mere shell and the lower half was studded with abscesses and contained many stones. There was a small perinephritic abscess. The kidney was removed and the patient has enjoyed good health ever since.

Fig. 12. Complete unilateral duplication. Note the congenitally small upper pelvis (author’s case).


CASE 19

‘A man, aged twenty-nine, with diffuse upper abdominal pain. The history was of a gall bladder disturbance. The bismuth series and gall bladder visualization were normal. A bilateral pyelogram showed a normal right kidney and a partial duplication of the left, the ureter dividing at the pelvic brim. The lower pelvis was large and the upper quite rudimentary. Laparotomy revealed a. distinctly pathological gall bladder which was removed, and the patient has been well ever since.


I have met with one anomaly of the ureteral lumen.

CASE 20

Cystoscopy showed two ureteral orifices normal in position. Each time a peristaltic wave swept down the left ureter, the lower end expanded to the size ‘of a small grape. This was possibly a congenital stricture of the ureteral orifice. The orifice was snipped with

scissors and kept dilated, and, when last heard of, the patient was well.

Fig. 13. Complete duplication on the right side and a partial duplication on- the left. Note that the upper part of the left kidney apparently has no pelvis (author ’s case).

I have had no cases of anomalies of implantation. In this case the ureter may be split off with the rectum; it may retain its connection with the lower end of the Wolffian duct, and so be found in the posterior urethra, ejaculatory duct, seminal: vesicles, etc.

Persistent Urachus

Persistent urachus is the remains of the allantois, which in the embryo extends from the bladder upwards to the umbilical cord. In the adult it is represented by a small, solid cord of connective tissue extending from the umbilicus to the bladder. There are four classes: com plete, blind internal, blind external and blind or cystic.

CASE 21

We saw a woman recently with a persistent discharge from the navel. Pressure in the midline below expelled a lot of sero-purulent material. Exploration showed a sinus of about two inches long in the midline running towards the p-ubes. Whether this was a persistent urachus I am not willing to say, but its position and character resembled a patent urachus of the blind external type.

EXTROVERSION on THE BLADDER

Extroversion of the bladder is not common and is one of the most distressing congenital anomalies" seen in apparently otherwise normal children. In these cases the whole anterior wall of the bladder is absent and the posterior wall is pushed out through a congenital defect in the anterior abdominal wall. In many cases there is little but the trigone present. The ureteric orifices may be seen, and on watching for a few seconds one sees urine Spurting . at intervals from them. There are two types. first, complete. The whole anterior wall of the bladder is missing. The symphysis pubis is not united and the penis is epispadic, the urethra being represented by a shallow trough. Second, incomplete. Here only a portion of the bladder wall is absent. The pubes is united and the penis is normal. These anomalies are commonly associated with others. I have seen three cases of extroversion. Two were in the wards of the General Hospital. fig. 14, taken from Young ’s Urology, because of its clearness illustrates some

Fig. 14. Complete epispadias and extroversion of bladder. (Young).

of the point spoken of. The cause of extroversion of the bladder is unknown. There are seve eral theories. first, that it was due to some congenital obstruction lower down and the bladder simply bursts; second, that it is due to pathological ulceration of the anterior abdominal wall. One man believes that it is due to a persistent blastophore. Others think that it’ has something to do with mal-development of the cloacal membrane. Others believe that it is due to a failure of the mesodermic plates to unite in the midline. That it is a congenital defect in growth is certain.

THE URETHRA Congenrital obstmction.——The most common type is a simple epithelial occlusion of the meatus. Any portion of the urethra, however, may be occluded by a small epithelial plug.

CASE 22

A new-born baby. For the first thirty-six hours no urine was passed. ‘There was‘ an obstruction one em. up the urethra, and a stifl’ filiform bougie was passed through this. The child was admitted to the hospital and urine was passed freely several times in the next day. The child has been well since.

Congenital va’lves.—These occur in the posterior urethra and are of three types‘. They


Fig. 15. Congenital valve of the urethra, similar to the author ’s case. V

(Young). 226


are folds or duplications of the mucous membrane of the urethra, which, during urination, balloon out much as do the valves in veins, and thus preventturination. Dr. Spooner and I have met with an example of this type in a new-born. baby. The condition is best shown in fig. 15. It will b.e seen here that the valve lies below the verumontanum. The second type rises upwards from the verumontanum and its upper end is fastened inside the sphincter of the bladder. “f The third type is a disk‘-shaped valve, its outer-edge being attached to the whole circumference of the urethra, the ‘only means of urination being through a small hole in —the centre. if if 0



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