OPEN ACCESSJacobs Journal of Nephrology and Urology

A Brief historical Survey of the Anatomophysiology of the KidneyS. Musitelli*

University of Pavia-Italy

*Corresponding author: Dr. S. Musitelli, 20080 ZIBIDO SAN GIACOMO (Mi) – ITALY, S.S. dei Giovi, n 69, Tel: + 39- 029053748,

Email: sergiomusitelli@libero.it

Received: 02-16-2018

Accepted: 02-28-2018

Published: 03-01-2018

Copyright: © 2018 Musitelli

Historical Article

Cite this article: Musitelli S. A Brief historical Survey of the Anatomophysiology of the Kidney. J J Nephro Urol. 2018, 5(1): 023.

Summary

None of the medical treatises of the must ancient civilizations (Mesopotamia, Ancient Egypt, China, India) contain any anatomo-physiological description of the kidney. Aristotle was the fist, who dealt with the matter. Aulus Cornelius Celsus describes the kidney in a brief passage of his De medicina. nothing interesting may be found in the treatises of the physicians of the Middle Ages till Berengarius of Carpi, who dissected from the concave side the multipapillary kidney (perhaps of a pig) and described for the first time the renal papillae. Vesalius dissected and described the monopapillary kidney of a dog and erroneously referred its structure to the human one. Gabriele Falloppio, Bartolomeo Eustachi and Caspar Bauhin improved the knowledge of the structure of the kidney, but could not describe it clearly enough owing to the lack of any idea of blood circulation and of any magnifying instrument. Nathanael Highmore – who advocated the blood circulation – gave a more advanced description, but had not even the faintest idea of what we call “nephron”, the history of the structure and the function of which was started by Lorenzo Bellini and improved every more by the subsequent anatomists (Malpighi, Ruysch, Schumlansky, Bertin, Müller, etc.) till William Bowmann, who finally succeeded in discovering the real structure of the nephron thanks to having nearly perfect microscopes at his disposal and having recourse to a double injection.

FOM THE ORIGINS TO ARISTOTLE

1.1 Not even the faintest description of the anatomical structure of the kidneys may be found in the medical texts of ancient Mesopotamian, ancient Egyptian, ancient Persian cultures and civilizations, or in the most ancient medical treatises of both the Chinese and the Indian cultures.

Although in some Assyrian and Babylonian tablets, as well as in some chapters of the so-called Egyptian Ebers’ and Kahun papyrus, in the most ancient passages of the Avesta (the holy Scripture of the ancient Persia), in the surely most ancient chapters of the Indian medical treatises called Ayurveda, of the Chinese Book of the Yellow Emperor and in the big treatises called Suçrutasamhita (i.e. “The way of Suçruta”) and Carakasamhita (i.e. The way of Caraka” [1]) after the two most famous Indian physicians Suçruta and Caraka (II century E.V.) one can find a lot of allusions to

different diseases of the urinary tract, nonetheless not even the faintest allusion to the anatomophysiology of the kidney may be found in any of these texts.

1.2 Aulus Cornelius Celsus (1st century B.C.-1st century A.D.) maintains [2] that “Hippocrates of Cos...first and foremost worthy to be remembered, notable both for professional skill and for eloquence,...separated this branch of learning (i.e. medicine) from the study of philosophy”. Indeed the “Hippocratic method” could be correctly summarized in three words: “observatio et ratio”, that is to say “rational elaboration of the data of experience”. However, in spite of the worldwide renown of the so-called Corpus Hippocraticum, apart from the fact that most probably none of the works of this collection may be ascribed to Hippocrates himself, not even the faintest description of the anatomophysiology of the urinary apparatus can be found in any of its 53 treatises and the corresponding about 72 books. Nonetheless some

Jacobs Publishers 2Aphorisms [3] like – for instance – IV, 75: “Blood or pus in the urine indicates ulceration of the kidneys or bladder”; IV, 76: “when the urine is thick, and small pieces of flesh-like hairs pass with it, it means a secretion from the kidneys”; IV, 78: “When a patient has a spontaneous discharge of blood and urine, it indicates the breaking of a small vein in the kidneys”: IV, 79: “When the urine contains a sandy sediment there is a stone in the bladder”, let us suppose that the Hippocratic physician had at least a rough idea that

1) the urine flowed from the kidneys into the bladder;

2) that the kidneys were provided with an inner cavity;

3) that the kidneys were also provided with veins [4] and ureters.

Aristotle and the Hellenistic anatomo-physiologists

One must wait Aristotle (384-322 B.C.) in order to find a specific and extensive description of the anatomophysiology of the kidney. He deals with this topic in a lot of more or less long chapters of his main anatomical and biological treatises [5]. However I think it better not to bore the reader with the quotation of all the passages and to confine myself to give him a brief but as complete and as faithful as possible summary of his statements. Apart from his mistake of describing the right kidney higher than the left [6], he maintains that:

1) the kidney consists of a dense substance;

2) the human kidney, as well as that of cows and oxen is formed by many little kidneys and this is why the treatment of a renal disease is exceptionally difficult, because it concerns a lot of little kidneys;

3) the kidneys serve the urinary bladder and this is why the animals without bladder (like snakes) have not kidneys, with the exception of some birds in which one may observe wide and flat bodies similar to kidneys [7];

4) the kidney is provided with branches of veins and arteries, although Aristotle does not yet distinguish between veins and arteries and confines himself to speaking of “big vein” (= our “vena cava”) and of “aorta” (= our “aorta”, a vein to him);

5) inside this dense substance there is a cavity (= our “pelvis”);

6) this cavity is directly connected with the bladder through the ureters;

7) no blood vessels reach the pelvis;

8) they dissipate and ramify in the dense substance;

9) this is proven by the fact that no blood clots may be found in the pelvis not even post mortem.

It will be clear that neither Aristotle nor – as we shall see below – Galen did ever allude to a sort of filtering mem-brane – later ridiculed by Vesalius - that divided the pelvis into an upper and a lower part, so that the thick venal blood would reach the upper one, its thinner substance would “filter” through this membrane, transform into urine and finally reach the bladder through the ureters (Figure 1).

Figure 1. The alleged “filtering membrane” ridiculed by Vesalius (1514-1564) in De humani corporis fabrica (Basel, 1543), V, 10, p. 515.

Indeed Aristotle’s statement is peremptory: no blood reaches the renal pelvis!

Unfortunately all the treatises of the great Hellenistic anato-mists – namely Herophilus and Erasistratus (flourished in the 2nd half of the 3rd century B.C.) – and we are forced to rely on Galen’s more or less ample and always indirect and polemical quotations. However although they must be always handled with great care, nonetheless they let us understand the most important characteristic of their thought: they tried to attempt a mechanistic and therefore “quantitative” interpretation of all the phenomena, which may be clearly represented by Erasis-tratus’ statement that “the heart is a pump”. As for the kidneys Galen argues with Erasistratus’ mechanistic ideas with the following passage [8]: “The example of milk being made into cheese will show clearly what I mean. For this, too, although it is all thrown into the wicker strainers, does not all percolate through; such part of it as is too fine in proportion to the width of the meshes passes downwards, and is called “serum”; the remaining thick portion which is destined to become cheese cannot get down, since the pores of the strainers will not ad-mit it” and concludes: “Thus it is that, if the blood -serum has similarly to percolate through the kidneys, the whole of the blood must come to them, and not merely one par of it”. By consequence Erasistratus’ interpretation cannot absolutely be

Jacobs Publishers 3accepted according to Galen, who has recourse to the four “vir-tues” each part of a living body is endowed with: attracting, retaining, transforming and expelling virtues.

The surely most brilliant and exceptionally advanced Helle-nistic “quantitative” perspective obtained excellent and real-ly wonderful results in physics, mechanics and mathematics [9], but failed in medicine. Indeed the lack of chemistry, the ignorance of blood circulation and the lack of any magnifying instrument prevented the Hellenistic anatomo-physiologists from explaining fundamental phenomena like respiration, digestion and generation. By consequence the “quantitative” perspective was superseded by the “qualitative” and therefore “animistic” and “finalistic” one, which seemed to explain ev-erything, although, in fact, it explained nothing at all.

The “quantitative” perspective will be finally renewed by Gali-leo Galilei’s (1564-1642) “scientific revolution”, which started all the branches of our modern science in general and – as we shall see below – of our modern anatomophysiology in partic-ular.

From Celsus To Galen

1.1 Aulus Cornelius Celsus deals with the anatomophysiology of the kidneys in the 4th book of his De medicina [10] “The kidneys – he writes – ...are separated: they adhere to the loins above the hips , being concave on the surface adhering to the hips and convex on the other; they are both vascular, have ventricles (i.e. pelvis and calices) and are covered by coats...From the kidneys, two veins, white in colour, lead to the bladder; the Greeks call them “ureters”, because they believe that through them the urine descending drops into the bladder.” The words “they believe” seem alluding to the absurd opinion of other not Greek physicians, mainly to Asclepiades of Prusa († about 40 B.C.) and to his disciple Themison of Laodicea: according to both the kidneys were absolutely useless and urine gathered into the bladder thanks to “evaporation” from the bowels!

Apart from these really absurd opinions, from the whole passages either quoted or faithfully summarized above one can easily conclude that all the authors – from Aristotle to Celsus – had clearly realized five fundamental facts:

1) veins and arteries reached [11] the kidneys but their branches spread through the renal substance and did not reach the pelvis;

2) the internal cavity of the kidneys is only one and is provided with inlets, i.e. the calices;

3) the internal surface of the pelvis is provided with a “panniculus” which forms the ureters;

4) the external surface of the kidneys is covered by

the cortical membrane;

5) into the pelvis and mainly into the calices stones frequently form.

As for Galen (c. 129-199 A.D.) some brief premises are necessary:

1) he was aware of the difference between veins and arteries but not of blood circulation;

2) he refused the Hellenistic “quantitative” perspective and advocated the “qualitative” one;

3) as he – as well as all the previous and subsequent authors till the 18th century had not even the faintest idea of “chemistry” [12], he was forced to have recourse to the “vir-tues” (attracting, retaining, transforming and expelling), to the “spirits” (natural, vital and animal), to the “four qualities” – as Aristotle had maintained – that characterized each part of a living body (hot, dry, cold and wet), to Aristotle’s “four ele-ments ” (earth, water, air and fire), and “four humours” (blood, phlegm, yellow bile and black bile) the balance of which cor-responded to “health”, whilst their imbalance caused diseases.

These ideas may be represented by the following two fig-ures (Figure 2 and Figure 3) [13]:

Figure 2. The correspondence of “qualities”, “elements” and “hu-mours” according to Aristotle and Galen.

Jacobs Publishers 4

Figure 3. Galen’s anatomo-physiological system.

Galen deals with the anatomophysiology of the kidney in a lot of passages of his most important anatomical and physiolog-ical treatises, i.e. in DE usu partium corporis humani (On the usefulness of the parts of the human body) in 17 books, and Anatomicae administrationes (Anatomical procedures) in 15 books [14].

As Galen is always exceptionally verbose and prolix, and gen-erally does nothing else than developing Aristotle’s statements (and even his mistakes!), I will confine myself to quoting only the most interesting passages and to give the reader an as faithful as possible summary of his theories.

Let us begin with A.A. VI, 13, K. II, 579 ff. [15]: “Let us now deal with the kidneys – he writes – the right of which is higher than the left [16] in all animals and adheres to the major lobe of the liver. Big blood vessels starting from the vena cava and the aorta reach them...In big animals you will succeed in inserting a probe till the internal cavity. You will also clearly realize that each of the above mentioned vessels...that the internal cavity of the kidney is covered with a membrane and that this mem-brane, in a point not far from the insertion of the blood vessels shows another long duct...The orifice of this duct may be easy seen even if the animal is not so big. You can insert a thin probe either from the internal cavity, after having cut the kidney [17], or from the external orifice of this duct, which is called “ureter” and consists of a tunic of his own”.

It is clear that Galen never described the filtering membrane ridiculed by Vesalius! Moreover it is also clear that he, in ac-cordance with Aristotle, maintains peremptorily that no blood reaches the pelvis.

Indeed, according to him, urine was filtered by a “panniculus”, i.e. a close network of arterial and venous capillaries covering the internal wall of the pelvis.

All the subsequent authors – Vesalius included – misunder-stood Galen statement and mistook this “panniculus” for a fil-tering membrane that spread out at the middle of the pelvis and divided it into an upper and a lower cavity: blood gathered in the higher and urine in the lower one!

Galen’s thought is wonderfully summarize in a passage of the pseudo-galenic treatise “On the diagnosis and the treatment of the diseases of the kidneys” [18]: “The substance of the kidneys – the anonymous author writes – is peculiar and has nothing to do with the substance of any other part. It consists of fibres and flesh, but the flesh is thick. It was done by nature to pre-vent the blood that reaches it from flowing too quickly while it is still mixed with urine. This fleshy substance is provided with many inlets and as in each inlet of this substance stones form, these stones cause terrible pains...As for the shape of the kid-neys, it is sigmoid [19]. At he middle of the substance there is a cavity...some of the major veins and a lot of venous capillaries reach the internal cavity, where they disappear in the adhering membrane”.

I suppose that everyone can observe that not even the faintest description of the “filter” ridiculed by Vesalius may be found in any of the ancient Greek and Latin anatomists.

It was absurdly described by the anatomists of the Middle Ages and was the result of a superficial misinterpretation of Aristo-tle’s and Galen’s texts.

The middle ages

Nothing else and nothing more may be found in the more or less ample treatises of the physicians and anatomists of the Middle Ages. Suffice it reading the two really pitiful “anatom-ical” lessons entitled “Anatomia porci”, one written by Copho the Younger († in 1110) [20], the second by an anonymous au-thor, who argues against Copho [21].

If these “lessons” are pitiful, even more pitiful are the anato-mo-physiological passages one can read in that shameful amount of nonsense that forms the unmeritedly famous “Reg-imen sanitatis Salenitanum” (or Flos Medicinae) [22]. These texts let us realize the total decadence of the anatomo-physi-ological studies and knowledge that occurred at least from the 4th to the 15th century.

This being the facts, I think that it is better to say with Dante Alighieri (1265-1321) “non ragioniam di lor, ma guarda e pas-sa” (let us not speak of hem, but look at them and pass over) [23].

Jacobs Publishers 5From Mundinus to Berengarius of Carpi

All the historians of Medicine award Mondinus (or “Raimun-dinus”) de’ Liucci (or “Liuzzi”) (c. 1270-1326) the merit of having renewed the study and the teaching of anatomy at the University of Bologna, where he held the Chair of Anatomy from 1321 to 1324. In fact he studied and taught anatomy on the basis of autopsies of human corpses. However he dissected only two female corpses in 1315 and published his Anothomia (sic!) in 1316. In spite of its exceptional fame [24] the book is nothing else than a summary of Galen’s anatomophysiology, Galen’s mistakes included [25].

Mundinus deals with the anatomophysiology of the kidneys in the chapter De anothomia duarum emulgentium renum (Anatomy of the two emulgent veins of the kidneys) in which although he repeats and summarizes Galen’s descriptions, nonetheless he does not misinterpret the “panniculus” and correctly maintains that it is a close network of arterial and venous capillaries covering the internal wall of the pelvis [26].

Suffice it to read one only passage [27]: “It is clear that the urine reaches the kidneys still mixed with blood whilst it reaches the bladder purified and separated from the blood. By consequence it must be strained and purified in the kidneys. It is strained because it reaches the renal cavity, that you can see cutting the kidney from the convex side – not from the concave one – by a longitudinal incision so deep as to reach the cavi-ty. You will see immediately a “panniculus”, i.e. a sort of loose cloth. It is the renal vein that rarefied like a filter. Urine, but not blood, can flow through these porosities. This being the fact, urine oozes into the lower part of the kidney towards the ori-fice whence the so-called ureter lengthens till the bladder”.

Well then, what does it mean “into the lower part”? Every learned man – from Hippocrates to Mundinus as well as ev-ery learned man of our times, let alone every mathematician – knew and knows that the lowest point of a sphere or of any concave body is the centre. This being the fact, the “lower part” of the kidney is just its centre, i.e. the pelvis [28]. This means that “into the lower part” does not at all mean “into the lower cavity from the upper one” but simply “into the internal cavity of the kidney”, i.e. “into the pelvis”!

The same correct statement may be found in Gabriele Zerbi’s (1445-1505) Liber anatomie (sic!) corporis humani et singu-lorum membrorum illius (Book on the anatomy of the human body and on each of its parts). In an “Additio” to the treatise he writes: “what I have written above clearly proves the mistake of those, who describe the transversal “filtering panniculus”.

The first and fundamental step towards what we can rightly call “the modern kidney” was made by Berengarius of Carpi (1470-1530), who really revolutionized the anatomophysiol-ogy of the kidneys in the chapters CXXVII-CXXX of his Carpi

commentaria cum amplissimis additionibus super Anatomia Mundini una cum textu eiusdem in pristinum et verum ni-torem redacto (Carpi’s commentaries on Mundinus’ Anatomy with very ample additions and together with its text restored to the original and corrected writing) printed in Bologna in 1521.

His “revolution” concerns both the method and the consequent discoveries.

As for the method, he had recourse for the first time not to the simple “experience” but to real “experiments”, anticipating – as we have pointed out above and shall see later – Galileo Galilei’s method.

Suffice it to read the first wonderful passage of his “Commen-taries”, which clearly illustrates the new method. After having observed the disparity of Mundinus’ and Zerbi’s opinion from the one hand and, on the other hand, Ferrari da Gradi’s one, he writes: “I thought that it was advisable to examine the anato-my of the human kidneys as well as those of the pig and other animals as carefully as possible. and had recourse to the fol-lowing means in performing the anatomical procedure: I took some kidneys and injected hot water through the renal vein with a syringe in order to realize if it entered the pelvis pushing the water violently. I observed that the water did not enter the pelvis and the kidney was filled by water and became excep-tionally swollen. After having observed this fact, I incised the surface of the kidney, injected again hot water into it through the renal vein and realized that the injected water flowed from the incision. After having performed this experiment, I cut the ureter till the renal cavity and realized that the ureter widens like a basin at the middle of the renal substance along the lon-gitudinal axis of the kidney and stones form just into this basin in my opinion”.

It is worth emphasizing the most important particular of this passage: Berengarius realizes that it is not the internal wall of the pelvis that forms the ureter – as all the previous anatomists from Aristotle to Galen and all the subsequent ones thought – but is the ureter that widens and forms the internal wall of the pelvis.

But it is not jet enough. Berengarius goes on describing his fur-ther anatomical procedures and his further really wonderful observations and writes: “After having incised the ureter I in-serted again the syringe into the renal vein of the same opened and dissected kidney. Pushing the water by the syringe, the water flowed from the cut renal substance in the zone around the ureter as well as through the inner tract of the ureter itself. However – to say the truth – a greater amount of water flowed from the cavity that the ureter forms entering the kidney than that flowing through its fleshy part. Into that cavity formed by the ureter there are certain fleshy protuberances that look like the nipples of the female bosom. However they are littler

Jacobs Publishers 6and the water I had previously injected into the renal vein by the syringe flowed around these fleshy protuberances. At this point I wanted to realize as carefully as possible through which way that water flowed towards the ureter from the renal vein and observed that the renal vein branched out into ever thin-ner capillaries and saw that the thinnest ones run towards the external part of the kidney, whilst some of them turned towards the ureter or better towards the above mentioned protuberances that look like the nipples of the female bosom [29]. I also observed that such venous capillaries that bring the urine to the above mentioned cavity formed by the ureter end-ed around the fleshy protuberances. The base of these fleshy protuberances lies on the ends of the venous capillaries whilst their cusp faces the cavity formed by the ureter...On the other hand I supposed that urine oozed from those protuberances like milk oozes from the female nipples. However I did not suc-ceed in realizing this fact”.

I think the reader will agree that these passages are really wonderful and that there cannot be any doubt that Berengar-ius made the first and astonishing step towards our “modern kidney”.

sA I think that repeating the ancient anatomical procedures [30] (be they either clearly described or inducible from their statements makes no difference) is the fundamental means to understand the real meaning of the different statements, I have repeated the anatomical procedure described in the second of Berengarius’ passages and the result confirms wonderfully his observations (Figure 4):

Figure 4. The kidney of a pig as described by Berengarius. His “pro-tuberances that kook like the nipples of the female bosom” are clearly evident.

Berengariu’s statements were confirmed by Niccolò Massa (1499-1569) in his Anatomiae liber introductorius (Introduc-tory book on Anomy) printed in Venice in 1536, that is to say fifteen years after Berengarius’ “Commentaries”.

However one must wonder that, in spite of his exceptional carefulness, Massa is still maintaining that the right kidney is higher than the left [31]!

From BERENGARIUS of Carpi to Nathanael Highmore.

Some premises are necessary before dealing with Andrea Ve-salius’ anatomo- physiology of the kidneys [32]:

1. he ignored blood circulation;

2. he had not even the faintest idea of chemistry;

3. he had no magnifying instrument at his disposal;

4. he ignored Berengarius’ not only wonderful achievements but also his revolutionary method and went on dissecting the kidneys from the convex side;

5. in spite of his sometimes even too violent debates against Galen, he is still a “galenist” and has still recourse to the “spir-its” and the “longitudinal, oblique and transversal fibres” en-dowed wit the attractive, retaining, transforming and expelling “virtues” [33];

6. He performed autopsies of human corpses – this is true – but in many cases, and mainly – as I shall emphasize below – in the case of the kidneys (as pointed out by Falloppio) he had recourse to parts of animals and referred his observations to the corresponding parts of the human body. This is why one is forced to confess that his De humani corporis fabrica contains a lot of mistakes.

This being the fact, one cannot avoid agreeing with Gabriele Falloppio’s (1523-1562) statement [34]. In spite of the rev-erence he pays to his master, after having described his own anatomical observations concerning the kidneys [35] and having also pointed out that Vesalius dissected dog’s kidneys, he writes: “this is the real structure of the human kidney, but not of the dog’s or goat’s one...if only my master Vesalius was aware of this! Indeed he would not so easily fail either about the larynx, or about the tongue, or about the eye, rather de-ceived by oxen’s and other animal’s parts that he dissected and illustrated instead of the human ones, than owing either to negligence or to crudeness of mind...Indeed in the dissection of the human kidney he feared too much the fat, although, on the contrary, it is not so formidable”.

At any rate Vesalius dissected the monopapillary kidney of dogs because “it appears emaciated and completely free from the fat one may observe in the human kidney” and cut it – as said above – from the convex side, abraded first a part of the unique papilla, then the entire papilla and emphasized the off-shoots of the membranous body till the arcuate venous and ar-terial vessels. Indeed if one repeats Vesalius’ anatomical proce-dure, he can observe that both the front and the rear offshoots of the membranous body run laterally, do not reach the surface of the kidney but stop at what we call “limit between medullar and cortical substance”, In this zone the front offshoots bend

Jacobs Publishers 7back, the rear ones bend in front, anastomose “as if they were – Vesalius writes – a unique and identical body” and “form a cavity bounded by both the offshoots”.

He illustrates the results of his anatomical procedure in the fol-lowing three figures (Figure 5) [36]:

1 2 3

Figure 5. Vesalius’ anatomic procedures of the monopapillary kidney of a dog: 1) the papilla looks like a dissected semilunar septum; 2) after having partly eliminated its two half parts, the cavity of the pel-vis (second “sinus” to Vesalius) appears more clearly bounded by the membranous body and by its offshoots, the initial tracts of which can be seen; 3) after having completely eliminated the two half parts of the papilla, the offshoots of the membranous body are emphasized till the arches that form what Vesalius calls “first sinus” [37].

I have repeated Vesalius’ anatomic procedures having recourse to the monopapillary kidney of a kid and the results clearly correspond to Vesalius’ figures (Figure 6):

1 2

3

Figure 6. The three figures of my anatomic procedures representing Vesalius’ illustrations.

No doubt Vesalius – in spite of his many mistakes – must be awarded the merit of having refused the “principle of author-ity” and advocated observation and experience as the only method of study. His example will be exceptionally fruitful – this is true – but his method will soon turn against him.

Gabriele Falloppio’s (1523-1562) Observationes anatomicae (Venice, 1561) prove this topic. Indeed, the few pages of his treatise show the calibre of his anatomical acumen [38]. “If you want, my dear Peter[39], to achieve a right knowledge of this sinus (i.e. the pelvis) beware carefully of beginning dissecting [the kidney] from the back side, that is to say from its convex part, but insert a probe into the ureter, rise with the lancet till that sinus and, at the same time, divide the concave side of the kidney longitudinally from upwards to downwards”. Thanks to this method, Falloppio – who dissected also multipapillar human kidneys – succeeded in realizing that the pelvis “is pro-vided with ducts or thin tubules, like if it had pervious fingers; in each of these tubules you find a fleshy operculum that looks like a wart. A little tract of this operculum penetrates into the tubule, occludes it and causes the dripping of the urine. Indeed this operculum consists of the same substance of the kidney, which reaches that duct or tube in order to let the urine flow into the internal cavity”.

Although Falloppio’s observations and descriptions quoted above are really wonderful, nonetheless his most important achievement is the complete vascularization of the kidney. Suf-fice it to read another and no less wonderful passage: “Every-one may realize – he writes – ...that veins and arteries spread into the renal substance and body till the external surface. Indeed I do not succeed in finding in the human kidney the external, vascular and perforated sinus alleged by Vesalius...By contrast I see that just these conspicuous vessels spread through the entire flesh of these viscera, and – as for veins and arteries – that their substance thins out in the kidneys like the vessels that spread in the brain. This thinness that predisposes to laceration and makes it difficult to emphasize these vessels was most probably the cause why they did not draw the atten-tion of the anatomists”. If the veins and the arteries reach the external surface of the kidney, on the other hand Falloppio has observed that “... contrary to the opinion of the other anato-mists, straight meatus cross the whole renal substance from the external surface till the middle sinus and everyone may see these meatus. This being the fact, it is necessary to recognize that a fibrous body exists in the kidneys, because every body provided with a lot of long and well ordered meatus consists necessarily of fibres. However the other anatomists do not agree with my opinion. I leave it to you to ascertain whether these fibres are nervous or fleshy, or if they consist of both the substances”.

As we shall see below, the solution of this problem will be fronted by Lorenzo Bellini (1643-1704).

Jacobs Publishers 8Falloppio’s Observationes were printed – as said above [40] - in Venice in 1561. On December 27th of the same year Vesalius, while in Madrid, wrote an Anatomicarum Gabrielis Falloppii observationum examen (Discussion on Gabriele Falloppio’s Anatomic observations), but the work was only printed in 1564, when Vesalius had already started for Holy Land whence he never came back.

I think it useless to spend time about this rather miserable work and confine myself to agreeing with Moritz Holl (1823-1920) [41], who pointed out quite correctly that Vesalius mis-took the offshoots of the membranous body he had observed, described and illustrated in the monopapillary kidney of a dog for the calyces discovered by Falloppio in the multipapillary human kidney.

The fundamental differences between the multipapillary hu-man kidney and the monopapillary one were most clearly em-phasized by Bartolomeo Eustachi (c. 1510-1574), who not only confirmed Berengarius’ statements dissecting human kidneys, but also tried and at least partly succeeded in highlighting the course of the venal and arterial branches in the multipapillary kidney, which he illustrated in the 5th plate of his Libellus de re-nibus (Booklet on the kidneys) [42] printed in Venice in 1563 and reprinted in his Opuscula anatomica (Venice, 1564) (Fig-ure 7).

Figure 7. The figures 11 and 12 of Eustachi’s V plate.

I think that reading even only Eustachi’s captions to these two figures will give the reader an idea of his exceptional mental acuity as well as of the no less exceptional subtlety of his sight so hat he will be surely forced to agree with Marcello Malpighi , according to whom [43] “There is no doubt that should Eu-stachi have had recourse not only to the knife, but also to a microscope and to injections of liquids (which he had recourse

to only in the study of the kidneys), he would have dissuaded all the posterity from the study of anatomy”. His captions read as follows: Figure 11 (which represents a longitudinal medi-al section from the convex side) shows the “caruncles, which protrude like sharp glands or nipples and close the open and pervious branches of the urinary duct; they are divided longi-tudinally in order to emphasize their lines that fray running from the centre to the circumference so that such caruncles look like if they consisted of a lot of gathered fibres”; Figure 12 represents the final branches of the venal and arterial vessels, which “subdivide in various ways through the renal substance, interlock and join with each other and, at last, end in thinnest and nearly invisible capillaries. Indeed if one presses the dis-sected kidney many blood drops appear, which prove that in-visible vessels are dispersed into the renal substance”.

Although many subsequent anatomists like André du Lau-rens († 1609), Caspar Bauhin (1560-1624), Johann Vesling (1598-1649) and Thomas Bartholin (1616-1680) proceeded in Eustachi’s footsteps and will be quoted by Lorenzo Bellini, nonetheless none of them made valuable contributions to the anatomo-physiological knowledge of the kidney.

Only one of Caspar Bauhin’s “Icones aiquot ex libro Naturae, praeter communem anatomicorum sententian desumptae” (Some images gathered from the book of Nature in contrast with the general opinion of the anatomists) [44] (Figure 8)

Figure 8. It represents the vascular scheme of the kidney obtained by scarification of the viscus [45], as Bauhin maintains: “Vasorum renis dextri a parenchymate separatorum delineatio” (Image of the vessels of the right kidney separated from the parenchyma).

Although it is more realistic than Eustachi’s figure [46], no-body can avoid observing that, in fact, it corresponds exactly to Eustachi’s one, although Bauhin refrains from quoting him. However the fact that Bauhin’s captions repeat Eustachi’s ones word for word is a clear proof of his rather dishonest behaviour.

Although the discovery of blood circulation [47] was as vio-lently as dully thwarted by many anatomists, and mainly by Thomas Bartholin and his school, it was enthusiastically advo-

cated by Nathanael Highmore in his Corporis humani disquisi-tio Anatomica in qua sanguinis circulationem in quavis Corpo-ris parte, plurimis typis ac aenigmatum Medicorum succincta dilucidatione ornatam prosequutus est Nathanael Highmorus (Anatomical disquisition about the human body, in which Na-thanael Highmore has emphasized the blood circulation in ev-ery part of the body adding a lot of figures and a brief expla-nation of physicians’ enigmas), Hague Comitis (= L’Aja), 1651.

Suffice it to observe the VIII and the IX plates of the chapter on the kidney (Figure 9 and Figure 10) and read at least some parts of his captions:

Figure 9. It represents the vascular skeleton of a human kidney after the abrasion of the renal parenchyma: “from the arcuate venous and arterial vessels” – according to him – an arterial and venous anasto-motic network starts, the meshes of which are “the spaces by which the serum (i.e. the urine) pushed out of the vessels thanks to exu-dation drips into the pelvis through the parenchyma that fills those empty spaces”.

Figure 10. It represents the same venous-arterial anastomotic net-work in the monopapillary kidney of a sheep.

As everyone can realize, Highmore succeeded in emphasizing clearly the vascular network placed between the medullar and the cortical substance that was foreshadowed by Vesa-lius. Although his observations and descriptions of the renal parenchyma are still rather backward-looking, nonetheless he made a fundamental progress and paved the way for Lorenzo Bellini’s (1643-1704) Exercitatio anatomica de strctura et usu renum (Anatomical research on the structure and function of the kidneys) (Florence, 1662).

The Galilean Revolution

Galileo Galilei writes in his treatise Il saggiatore (The assayer) [48]: “Philosophy[49] is written in this greatest book that stays always open before our eyes (I mean the Universe), but it can-not be understood without learning in advance both the lan-guage and the characters in which it is written. It is written in mathematical language and its characters are triangles, circles and other geometric figures: without these means it is abso-lutely impossible for a man to understand even one only word. Without them we are forced to hang uselessly about an ob-scure labyrinth”. Moreover he adds [50]: “As soon as I conceive of a matter or a concrete substance, I cannot avoid conceiving at the same time that it has this or that geometric shape, that it is big or little, with respect to others, that it is in this or that place, that it moves or rests, that it is or is not in contact with another concrete thing, that it is one, or more than one...But I feel not bound at all to conceive it as white, or red, bitter or sweet, resonant or dumb; and my reason could never conceive it endowed with such qualities, without the aid of the senses”.

It is clear hat that Galileo inaugurated a “quantitative” perspec-tive, demolished the “qualitative” one once for ever and paved

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the way for our modern science.

This new perspective had it roots in a fundamental event: in 1417 Poggio Bracciolini (2380-1459) had discovered Titus Lucretius Carus’ (c.94-55 B.C.) poem De rerum natura (On Nature), in which the great Latin poet advocates the “atomis-tic” and therefore “mechanistic” theory of Epicurus (342/41-271/70 B.C.).

The “mechanistic” perception of all the phenomena spread fast through the whole European culture [51] and was not only ad-vocated but also exceptionally improved by Galileo, but was also transferred to medicine in general and to physiology in particular by Giovanni Alfonso Borelli – the founder of the “iat-romechanic school” and master of both Bellini and Malpighi – to whom each and every living body was a “machine”, all the movements of which are explained by geometrical principles in his De motu anmaliun (On the movement of animals) (Fig-ure 11).

Figure 11. The 4th plate of Borelli’s De motu animalium.

If very living body is not a “fabrica”, but a “machina” it necessar-ily consists of a lot of ever littler “machinulae” till the minimal ones, the observation of which needs a magnifying instrument: the new scientific perspective led to the invention of the mi-croscope, which, on its turn, will force the scientists in general and the anatomists and physiologists in particular to front ever newer problems and therefore to improve an ever further and more complete knowledge.

From Bellini To Ruysch

Lorenzo Bellini was only 19 years old when he printed his wonderful Exrcitatio anatonica in which he traces the fibrous

structure of the kidney to an aggregate of canaliculi, or tubules, that run through the viscus from the external surface to the margin of the papillary body, where their meatus open as prov-en by the droplets that appear squeezing the kidney. He em-phasized the “sinuli” (later called “ductus belliniani” after him) in the venous network of the external surface of the kidney by injecting black liquid. According to him they consist of the tri-ple joining of arterial capillaries (i.e. the interlobular arteries), venous capillaries (i.e. the interlobular veins) and uriniferous tubules. The separation of the arterial blood into two parts oc-curs just into the “sinulus”: from the one hand the superfluous serum is aspirated into the uriniferous tubules thanks to capil-larity [52] (due to the different size of the ducts) and squeezed into the pelvis thanks to the movements of the diaphragm; on the other hand the purified blood penetrates into the venous capillaries [53].

I think that the reader will have a clearest idea of Bellini’s anatomical procedure as well as of his observations and dis-coveries if he only looks at the three plates, by which Bellini illustrated the whole matter (Figures 12-14) and considers the summaries of his pertinent captions I have added:

Figure 12: 1) The kidney of a ram dissected longitudinally from the concave side: A.A.: the major branches of the emulgent artery; B.B.: the major branches of the emulgent vein; C.C.: the division of the ar-tery into many and thinner ducts; D.D.: other arterial capillaries that proceed from the above mentioned “sinuli”; E.E.: final filaments of the fibrous flesh that end in the surface of the kidney; N.N.: the thin branches of the emulgent vein; O.O.: the minor vessels that Highmore likens to honeycombs [54]; 2) the same kidney, in which the fibrous flesh that overhangs the pelvis has been scarified; 3) Te same kidney cut longitudinally in order to show the joint of the fibrous flesh with the pelvis; 4) the tips of the renal ducts that forms the papillary body connected with the pelvis.

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Figure 13:5) a portion of the papillary body seen through the micro-scope and squeezed by the fingers; 6) the surface of the same kidney as it appears through the microscope after the injection of coloured liquid: A.A.: the surface of the kidney; B.B.: empty little spaces; C.C.: certain vermicular and tortuous “sinuli” (the so-called “ductus bell-iniani”), which surround the little empty spaces and from which the injected liquid oozes; 7) a human kidney cut longitudinally from the ureter to the pelvis. A.A.A.A.: the dissected kidney; B. the half ureter bent left: D.: a branch of the emulgent vein; E.: a branch of the emul-gent artery; G.G.: the open pelvis; H.H.H.: some portions of the pap-illary body that can be seen from the calices; I.: the beginning of the ureter.

Figure 14: 8) a half human kidney freed from the pelvis and the ma-jor part of the vessels in order to emphasize the tortuous joining of the renal ducts. A.A.: the farthest filaments that end at the external surface of the kidney; B.B.B.: the conjunction of the renal ducts that form the tortuous papillary body; C.C.C.: drops of serum that flow from the papillary body after being squeezed by the fingers; 9) a sep-arated portion of the papilla. A.A.: the tips of the fibres that reach the

surface of the kidney; B.B.: the whitish part of the same papilla, from which the C.C. little drops flow; 10) the whitish portion of the papilla of the kidney of a stag separated from the rest of kidney. A.: its whit-ish part from which the serum leaks; B.: its continuous filaments that run from the pelvis till the surface of the kidney. 11) The vessels of the kidney of a stag dissected longitudinally from the convex side and scarified. A.A.: the pelvis; B.B.B.B.: its prolongations and offshoots that cover the emulgent vessels; C.C.C.: the vessels that liken honeycombs; D.D.D.: the capillary vessels that reach the surface of the kidney.

There is no doubt the discovery of the so-called “ductus bell-iniani” started a new stage of the history of the knowledge of the renal structure. Indeed Bellini’s fundamental contribution was appreciated by Marcello Malpighi four years later in his De renibus (Bologna, 1666) [55].

The new perception of a living body as a “machina” is clear-ly phrased by Malpighi in a passage of his Risposta del Dottor Marcelllo Malpighi alla lettera “De recentiorum medicorum studio dissertatio epistolaris ad amicum (Dr. Marcello Mal-pighi’s response to the letter entitled “An epistolary disserta-tion on the study of the more recent physicians addressed to a friend) [56]. The passage reads as follows: “I am aware that nobody can understand the means, to which our soul has re-course to perform its acts, however it is sure that in the acts of vegetation, of the senses and the movements, the soul is forced to act in accordance with the machine it is applied to, like in the case either of a clock or of a mill, that is moved either by a lead or stone pendulum or by a beast or by a man; indeed even if an angel would move it, he would be forced to do the same variations of place that the beasts do. This is why, as I ignore how the angel acts, but I know the exact structure of the mill, I would understand such movements and such acts and should the mill malfunction, I would try to remedy its broken gears and let any else speak about the angel”. It is clear that after Galileo and till nowadays Science divorced – thank God! – Phi-losophy and Religion and went on along a way of its own.

In his De renibus Malpighi masterly developed Bellini’s contri-butions about the canalicular structure of the kidney and dis-covered by exceptionally skilful injections of Indian ink mixed with spirit of wine not only the twisted course of the tubule into the cortical substance of the kidney [57], but also the pres-ence of a lot of corpuscles (later called “malpighian corpuscles” after him [58]) hanging “veluti poma” (like apples) from the branches of the interlobular arteries. He interpreted these “corpuscles” under the perspective of his theory about the structure and the function of the glands: the “miliary gland” – in this case the renal “corpuscle” – consists of a membranous follicle surrounded by an anastomotic network of arteriove-nous capillaries, is provided with a nervous termination and reaches the excretory duct (Figure 15 and Figure 16):

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Figure 15. The “miliary gland” in a drawing made by Malpighi himself after having published his De renibus. The drawing is preserved in the Library of the University of Bologna. The “follicle” is surrounded by the arteriovenous network . The bent tract at right is the nerve. The vertical tube is the excretory duct.

Figure 16. The drawing of a “portion of human kidney”. Also this drawing is preserved in the Library of the University of Bologna and represents – as Malpighi writes – “the renal gland that consists of numberless follicles and as many fistulas that end in the middle of the “sinus”.

As for Malpighi’s explanation of diuresis – that forms the fee-blest and most unacceptable part of his treatise [59] - it is the result of fermentation of the blood thanks to which the par-ticles that it contains and must be eliminated acquire figures and sizes in proportion with those that exist just in the points, in which the membrane of the capillary vessels is in contact with the membrane of the glandular follicle [60].

In spite of this erroneous theory concerning the mechanism of diuresis, everyone will agree that Malpighi must be award-ed the exceptional merit of having discovered and described the “malpighian corpuscles” that were masterly and perfectly emphasized by Felice Grondona [61] having recourse to Mal-pighi’s anatomical procedure (Figures 17 and Figure 18):

Figure 17. Medial and longitudinal section of a kid kidney after in-jection of Indian ink mixed with alcohol through the renal artery. In the emphasized tract (right) both the interlobular vessels and num-berless black points appear. The black points are just the “malpighian corpuscles” that the following Figure 18 shows most clearly .

Figure 18. The “malpighian corpuscles” that appear “hanging like ap-ples” from the branches of the interlobular arteries.

Malpighi’s statements about the structure of the kidneys were violently criticized by Frederik Ruysch (1638-1731). He op-posed to Malpighi’s doctrine about the glandular structure of the viscus his own theory: he maintained that the “malpighian corpuscles” only consist of continuous vessels that have only different nature, shape and task. This theory is mainly the re-sult of Ruysch’s method of anatomical procedure: he injected coloured waxes mixed with some mysterious liquid [62] into the blood vessels with such a skilfulness that he succeeded in observing that the secreting gland consists of a ball of arterio-venous capillaries and particular canaliculi and that the excre-tory tubules are nothing else than the continuation of the ar-teries without any interposed glandular follicle as maintained by Malpighi (Figure 19).

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Figure 19. Plate 4th of Ruysch’s Thesaurus anatomicus tertius (Am-sterdam, 1703) It represents a dissected human kidney after injec-tion of wax. Besides the arterial terminations, “which transform – as Ruysch writes – into the “ductus belliniani” [63] with a snake-like path” also many black little points are represented into the cortical substance that are “round corpuscles – as Ruysch maintains – that look like if they were miliary glands”.

At this point it is worth reading an exceptionally interesting passage [64] that summarizes most clearly Ruysch’s obser-vations and opinions. It reads as follows: “In this Thesaurus X one may find also preparations of a human kidney, in which clearly appears not only which an opinion one has to express about the alleged renal glands, but also what has deceived the researches of the renal structure, that is to say the fact that in studying the kidneys round corpuscles often appear, which may be mistaken for glands, whilst they are nothing else than the extreme offshoots of the thinnest and twisted arteries. Whenever the renal arteries are completely filled, they unwind and unfold like a ball of thread, so that they are not – as I have said above – particular formations covered with a particular thin and peculiar membrane. As the membrane is missing, they are wrongly called “glands”. However it is worth observing that such windings of the blood vessels can never be observed into the other viscera”.

Although there is non doubt that Ruysch’s discoveries paved the way for all the subsequent studies on the inner anatomi-cal structure of the kidney and the physiology of uropoiesis, nonetheless they were criticized – as we shall se below – by renowned anatomo-physiologists, mainly by Hermann Boeh-raave (1661-1738).

From Ruysch To Bowmann

A chemical analysis of the urine was performed by Hermann Boerhaave. After having examined urine chemically [65] he re-alized that urine consisted of water derived from the blood in the proportion of 9 parts out of 20 and that it also contained a slightly alkaline, but very acrid and volatile salt, decomposed oil and friable and unstable earth. Moreover he observed that Ruysch’s too forced injection presses the little glandular for-mations and hide them.

At any rate Boehraave’s fundamental discovery of the chemi-cal composition of urine paved the way for the new and final knowledge of uropoiesis.

As for uropoiesis, Boehraave proposes an eclectic theory: he recognizes the presence of both the “malpighian corpuscles” and a direct communication between the arteries and the urin-iferous tubules so that “the urine – as he writes – is secreted by a double apparatus: the more active is the glandular one; the simpler is Ruysch’s one”. The debate about the two doctrines will go on until Bowman’s (1816-1892) discovery of the glo-merular capsule. However he made a great mistake: he main-tained that the thinner urine is eliminated through Ruysch’ tu-bules, and the thicker one through the glands, whilst it occurs just the contrary as Bertin will point out.

Indeed two French anatomists reverted to the study of the re-nal structure in the 18th century, namely Exupère-Joseph Ber-tin (1712-1781) and Antoine Ferrein (1693-1769). The name of Bertin is connected with the discovery of the columns of re-nal substance that insinuate between the pyramids and reach the renal sinus [66] (Fig. 20)

Figure 20. Bertin’s plate VI, figure 2: It represents – as Bertin writes in the caption – “the double apparatus of the organs that separate and filter the urine”. Ruysch’s snake-like ducts are contained into the black vascular stria; they bend from the circumference towards the centre and reach the excretory tubules. The bright striae represent the glan-dular masses formed by twisted tubules that reach the straight ones.

By conclusion, according to Bertin the renal structure consists 1) of a preponderant part (the bright striae) that, in its turn, consists of a tubular convolutions into which the glandular

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function occurs and secretes the thinner urine and 2) of much less relevant part consisting of exceptionally twisted blood vessels that are directly connected with the uriniferous and wider tubules [67], the task of which is secreting the thicker urine.

Antoine Ferrein, in his turn, reached his main results by study-ing – with the aid of the microscope and injections – the sur-faces of dilacerated, fresh kidneys of old and emaciated an-imals [68]. First of all he agrees with Malpighi [69] that the constitution of the kidney of the higher animals is plurilbated. Each lobe consists of both cortical and medullar substance, but the structure of the first is quite different from that described by Malpighi. Indeed if one observes the external surface of the kidney he can realize that it consists by nearly numberless lit-tle and whitish areas of different shapes, separated from each other and bounded by little and thin vessels. The shape of these little areas is either rounded or polygonal and their sub-stance consists of serpiginous tubules. Moreover Ferrein ob-serves that in the cortical portion of these apparent pyramids one may observe prolongations of medullar substance that form – so to say – its central axis. These prolongations enter the cortical cavities. that is to say that they appear complete-ly surrounded by the cortical substance. Ferrein illustrates his statements by plate XV, figures 4 and 5 (Figure 21):

Figure 21. Ferrein’s plate XV, figures 4 and 5: The medullar prolon-gations consisting of straight tubules push into the cortical substance and divide it into compartments filled with twisted tubules. These tu-bules form the renal gland and reach the medullar snake-like tubules (Figure 5), which in their turn reach the papillary tubules.

By conclusion, the cortical part of the kidney shows a glandu-lar structure. The medullar uriniferous tubules have not a rec-tilinear path, but a snake-like one till the papilla, where they become straight; one can observe that many of them bend up-wards and reach again the papilla.

By conclusion, Ferrein picks out a glandular structure and

function: the viscus is completely aglomerular and its excre-tory function is performed by “the white cortical tubule” – as he writes – through the wall of which thickest blood capillaries penetrate.

Apart from Luigi Galvani’s (1737-1798) discovery of the kid-neys of the birds [70], the study of the renal structure was resumed by the youngest Polish anatomist Alexander Schum-lansky (1748-1795), whose De structura renum tractatus physiologico-anatomicus, edente G.C.Wurtz, M.D., etc. (A phys-iological and anatomical treatise on the structure of the kid-neys) was published in Strasburg 1788.

I can summarize Schumlansky’s conclusions as follows: 1) the medullar ducts reach directly the twisted tubules, which end in correspondence of the glomerules; 2) the twisted tubules are as many as the vascular glomerules; 3) the twisted tubules only differ from the straight medullar ones with reference to their paths, 4) perhaps the twisted path has the task of slow-ing down the flow of the urine; 5) urine is secreted into the glomerule; 6) the ducts have the task of conveying it to the papilla; 7) however it is still unknown how the urine secreted into the glomerules can enter the tubules.

Schumlansky illustrated his observations in the 2nd plate of his treatise (Figure 22):

Figure 22.The 2nd plate of Schumlansky treatise: it represents an ideal diagram of a section that expands from the renal surface to the papilla and includes six Ferrein’s pyramids. Some twisted tubules end in correspondence with a glumerulus. The glumeruli are represented by little series around a vascular axis.

In 1818 Karl Wilhelm Eysenhardt (1794-1825) published in Berlin his treatise De structura renum observationes micro-scopicae (Microscopic observations on the structure of the kidneys). He identified a countless number of little oval, round and more or less close and grouped bodies; he supposed that

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they were just the “malpighian corpuscles” and had the task of secreting the urine. Schumlansky maintained that each gland was provided with a single excretory duct; by contrast Eysen-hardt maintains that exceptionally thin tubules radiate from each corpuscle and that these join with each other by num-berless anastomoses and originate a close network in which the corpuscles scatter. According to him this netlike shape may be observed in a fresh kidney as well as in those injected with coloured wax by Johan Nathanael Lieberkuhn (1711-17569) that were preserved in the Anatomical Museum of Berlin and that his master Karl Asmund Rudilphi (1777-1832) put at his disposal (Figures 23 and 24). The vessels of the medullar sub-stance originate from this thinnest network; they change their shape, become rectilinear and gather into fascicles that run to-wards the papilla.

Figure 23. The Figure 1 of the plate of Eysenhardt’s De sructura re-num: the cortical substance consists of “malpighian corpuscles” and a network of canaliculi that start from them. The network of the cortical canaliculi is joined to the straight tubules of the medullar substance. This figure derives from the observation of a fresh kidney.

Figure 24. The fig. 3 of the plate of Eysenhardt’s De sructura renum: it represents the same figure but derived from a microscopic prepara-tion of a kidney injected by Lieberkuhn.

3.2 In 1837 Joseph Berres (1796-1844) published his Anato-mie der mikroscopischen Gebilde des menschlichen Körpers (Anatomy of the microscopic structure of the human body) and illustrated his observations in plate X (Figure 25):

Figure 25. The 5th figure of Berres’ plate X: median network joins – in partial accordance with Ruysch – the efferent vessels that start from the glumerulus with the excretory tubules.

In 1828 Emil Huschke (1797-1858) published his Über die Textur derNieren (On the structure of the kidneys) and illus-trated the results of his observations in some figures of plate VIII of the treatise (Figure 26):

Figure 26. n. 1 represents the external surface of a kidney of a 3 months old baby: the uriniferous tubules filed by retrograde injection appear surrounded by a thinnest, thickest and regular network hat the author interpreted as a vascular network; n.2: represents the ex-ternal surface f the kidney of a duck filled with coloured wax by retro-grade injection and the aid of a pneumatic pump; n. 5 represents the subdivision of the uriniferous tubules in the kidney of a snack.

Probably Huschke had observed the deep injected tubular net-works similar to those observed and described later by Joseph Hyrtl (1811-1894).

The great German anatomist Johannes Müller (1801-1858) published his fundamental treatise De glandularum secer-nentium structura penitiori, earumque prima formatione in homine atque animalibus (On the deeper structure of the se-creting glands and their first formation in the man and in the animals) in Leipzig in 1830 [71].

He concluded that the kidney is a gland like the testicle, that is to say consisting of tubules; however the tubules of the kidney are infinitely thinner and softer.

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These ducts end into an ampullary dilatation provided with a blind bottom and are surrounded by a thinnest network of blood vessels. This being the fact, the task of the tubules is to secrete the urine. According to Müller too the “malpighian cor-puscles” are vascular formations that have not any connection with the uriniferous tubules, a mistake that will be pointed out by William Bowmann (1816-1892).

Müller illustrated his reports in 15 plates, the most important of which is plate XIV (Figure 27):

Figure 27. Plate XIV of Müller’s treatise: figure 4 represents the kid-ney of a squirrel: the kidney too is provided with tubules that end into a blind bottom like the testicle and show a path partly straight and partly snake-like. The glomerule is not an essential part of the urinary apparatus. Figure 6 and figure 7 are details of the kidney of a squirrel whilst the Figures 10-12 refer to the foetal kidney of a dolphin.

Jacob Henle (1809-1885), one of the best among Müller’s dis-ciples, will discover in 1862 the so-called “Henle’s loop” af-ter him. However he had already published a very important contribution in 1838: Über die Ausbreitung des epitelium im menschlichen Körper (On the propagation of the epithelium in the human body) [72]. In this work Henle developed the fun-damental concept of “coating epithelium” that covers both the external and the internal surfaces of the organism.

This being the fact, the membrane, of which – according to Malpighi –the glandular-tubular follicle of the kidney consists, shows a much more complex structure and results consist-ing of an external basal and an internal epithelial part, which consists of cells, whose task is just secreting urine. The new “cellular anatomy” started just from Henle’s observations and discoveries.

The foundation of the “cellular anatomy” was only possible thanks to having recourse to the new microscopes provided first with achromatic, then with oil-immersion objective [73]. These new magnification instruments eliminated both the chromatic aberrations and the optical illusions of the former microscopes, which deceived a lot of prior anatomists [74] .

The “cellular doctrine” was the starting-point of William Bow-mann’s researches and discoveries. Indeed he must be award-ed the particular merit of having finally and unequivocally solved the problem of the structure of the renal glomerule and its connections with the tubule [75].

He was aware of Louis Michel François Doyère’s (1811-1863) [76] method of double injection that lets one see even the sub-tlest vascular branches [77] and had recourse to it with bright-est results. He finally succeeded in finding the long-waited proof and uselessly researched by so many former researchers of the connection between the “malpighian corpuscle” and the uriniferous tubule.

Indeed Bowman could easily study – thanks to having recourse to the double injection and a good microscope – the afferent artery of the glomerule and emphasize both the vascular loops that form it and the efferent artery, However the most import-ant fact is that the injected liquids cause a serious damage to the capillary walls of the glomerule and break them; by con-sequence the liquid extravasates into the cavity of the capsule that enfolds the glomerular loops, fills them completely, enters the tubule and penetrates into a more or less long tract of its convolute part. Moreover the observation of preparations by the double injection let Bowmann point out that the efferent glomerular arteriole fray into a thin capillary network near the exit from the corpuscle and that this plexus surrounds the tubules along their complete path. This plexus is situated be-tween the efferent vessels of the “malpighian corpuscles” and the veins.

“Thus – he writes [78] – there are in the kidney two perfect-ly distinct systems of capillary vessels, through both of which the blood passes in its course from the arteries into the veins: the 1st, that inserted into the dilated extremities of the urinif-erous tubes, and in immediate connection with the arteries; the 2nd, that enveloping the convolutions of the tubes, and com-municating directly with the veins. The efferent vessels of the Malpighian bodies, that carry the blood between these two systems, may collectively be termed the “portal system” of the kidney. To these distinct capillary systems, I am inclined to at-tribute distinct parts of the function of the organ;... The former, which may be styled the Malpighian capillary system, is made up of as many parts as there are Malpighian bodies. These parts are entirely isolated from one another; and as there is no ino-sculation between the arterial branches supplying them, the blood enters each in a direct stream from the main trunk...The secreting tubes of the kidney, like those of all other glands, are, strictly speaking, an involution of the outer tegument of the frame: their interior is, in one sense, the outside of the body: their walls intervene between the vessels and the exterior. and, as it were, cover them in. But here is a tuft of capillaries extrud-ed through the wall of the tube, and lodged in a dilatation of its cavity, uncovered by any structure. Bare indeed, yet screened

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from injury in its remote cell, with infinite care and skill!...The other system of capillaries, or that surrounding the uriniferous tubes, corresponds, in every important respect, with that in-vesting the secreting canals of other glands”.

After having observed thinnest, fresh slices of kidney through a high-powered microscope (200-300 x) Bowman could iden-tify the structure of the tubule and describe perfectly the ep-ithelium and the basal membrane, which continue and forms the capsule that wraps the capillary ball: “As the Malpighian bodies – he writes[78] are placed in every possible direction, it often happens that a thin section , parallel to the neck of the tube, cannot at once be obtained: but with perseverance this may always be done. The capsule is then seen to pass off into the basement membrane of the tube, as the body of a Florence flask into its neck. The basement membrane of the tube is lined by a nucleated epithelium of a finely-granular opake aspect, while the neck of the tube and its orifice become abruptly cov-ered with a layer of cells much more transparent, and clothed with vibratile cilia. The epithelium is continued in many cases over the whole inner surface of the capsule; in other instances I have found it impossible to detect the slightest appearance of it over more than a third of the capsules”.

Conclusion

The main stages of the knowledge of the nephron were master-ly illustrated by Felice Grondona [79] with the following draw-ings (Figure 28)

Figure 28. The different stages of the knowledge of the nephron (af-ter Grondona)

Acknowledgment

The author is an Expert of the History Office of the E.A.U. (Eu-ropean Association of Urology). As miserable he is he dedi-cates this work to the memory of his adored son Giulio, whom a criminal driver who did not observe a STOP sign killed on May 14, 2012.

I cannot avoid expressing my unfortunately posthumous grat-itude to Prof. Luigi Belloni and Prof. Felice Grondona for all I learned from them and for their unforgettable friendship.

References

1. Read “Charka” like in “chapter”.

2. De Medicina, Prooemium,

3. Perhaps the only treatise of the Corpus Hippocraticum, at least a great part of which may not be ascribed to Hippocrates himself.

4. But it is worth remembering that the Hippocratic physician ignored the difference between arteries and veins.

5. The most important passages are the following: Historia an-imalium (Description of animals). I, 17, 496b34 ff,; III, 546b30 ff., and 670b23 ff.; De partibus animalium (Parts of animals), 9, 670b33ff and 671a34. The complete Greek text with an En-glish translation may be found in the Loeb Classical Library. It is worth emphasizing that Aristotle’s passages must always be quoted with: 1) title; 2) eventually book (in Roman numbers) and chapter (in Arabic numbers); 3) the Arabic number of the correspondent page in the “editio princeps” followed by “a” or “b” (the left and the right column respectively) and the number of the lines.

6. The mistake was repeated by Galen and all the subsequent anatomists and was corrected – as we shall see – only by Re-aldo Colombo (1516-1559) and his disciple Juan Valverde de Amusco (born c. 1520).

7. Galen described quite correctly the kidneys of the birds, but this exceptional statement was ignored until Luigi Galvani (1737-1798) re-discovered and re-described them.

8. Cf. On the natural faculties, I, 15, K., II, 58.

9. Suffice it to remember the achievements of Archimedes (287-212 B.C.): he invented a water-screw, discovered the laws of lever, the infinitesimal calculus, the specific gravity and the famous “Archimedes’ principle”.

10. Cf. 1,5 and 1, 10.

11. I say “reached” because all the anatomists prior to Wil-liam Harvey (1578-1657) and Marcello Malpighi (1628-1694) thought that the movements of both the arterial and the ve-nous blood were “centrifugal”: from the liver to all the parts of a living body and, finally, to the heart and from the heart again to all the parts.

12. It is worth remembering that “chemistry” was only cre-ated by the genius of Antoine Laurent Lavoisier (1743-1794).

13. Both after Ch. Singer and E.Ashworth Underwood: A short History of Medicine2, Oxford, at the Clarendon Press, 1962, p. 46 and p.64 respectively.

14. From now on referred as U.P. and A.A. respectively. The complete Greek text of U.P. has been preserved while Greek text of A.A. went lost from the 6th of the 9th book to the end. However the entire content of the lost books was preserved in an Arab translation of the whole treatise made by the disciples of Hunain ibn Ishaq (809- 873/77), the famous Joannitius (or Johannitius) of the authors of the Middle Ages.

15. All Galen’s texts are usually quoted by title, book(s), chap-ter(s), followed by K., a Roman number and an Arab one, re-ferring to Claudii Galeni opera quae extant omnia , Editionem curavit D. Carolus Gottlob Kühn, Lipsiae, Officina libraria Car. Cnoblochii, 1821 ff.

16. Aristotle’s mistake, as we have seen above. Cf. note n. 6.

17. It is worth observing that Both Aristotle and Galen, as well as all the subsequent anatomists cut the kidney from the con-vex part. As we shall see later, Berengarius of Carpi (16th cen-tury) was the first who cut he kidney from the concave part and his observations and descriptions started – so to say – the “modern kidney”.

18. Cf, K., XIX, 643 ff. The treatise was written in the 5th cen-tury.

19. That is to say they have the shape of a Greek “sigma”. In the ancient Greek alphabet the “sigma” was C. , and (at the end of a word) were created only in Byzantium in the 8th century.

20. It was published for the first time by Marcus Aurelius Sev-erinus (1580-1636) as an appendix to his “Zootomia democri-tea”(Democritean zootomy) (Nürnberg, 1645) and reprinted by Salvatore De Renzi in his Collectio Salernitana, Naples, Dalla Tipografia di Filiatre Sabezio, 1852 ff., II, p. 388 ff.

21.Cf, Salvatore De Renzi, Collectio Salernitana, etc., II, 388 ff.

22. Cf. Salvatore De Renzi, Collectio Salernitana, etc., I, 445 ff. and IV, 1 ff.

23. Cf. Divine Comedy, I, 3, 51.

24. His Anothomia was the official Anatomy book at least till the middle 16th century.

25. Suffice it to point out that he still maintains that the right kidney is higher than the left!

26. The first anatomist, who mistook Galen’s (and Mundinus’) correct statements about the “panniculus” was Gabriele Zer-bi (1445-1505), but Gian Matteo Ferrari da Gradi († in 1472) in the chapter “Anathomia renum” of his Practica medicinae

(Medical practice) (Padua, 1472) (cf. the columns 295vb-296ra) had already denied the presence of any “filtering mem-brane separating the pelvis into an upper and a lower cavity. Indeed in his Practica madicinae he correctly writes: “accord-ing to both truth and experience such a generally described “pannculus” cannot be found into the cavity o the kidneys”.

27. Cf. the pages 158v-159r of the edition printed in Venice in 1521 with Berengarius of Carpi’s “Commentaries” we shall deal with later.

28. It s worth remembering that in the Ptolemaic system the Earth occupies the lowest point of the spheres of the Universe, that is to say that it is just in their centre!

29.Berengarius is clearly describing the so-called “interlobu-lar veins”.

30. A method most genially inaugurated and advocated by the great Historian of Medicine Luigi Belloni (1914-1989). Cf. F. Grondona, La riprduzione degli esperimenti e delle osservazi-oni quale metodo per la storiografia della scienza (The repro-duction of the experiments and bservations as a method for the history of science), in Pubblicazioni di Storia della Scienza della Domus Galileiana, , Atti del convegno sui problemi di Sto-ria della Scienza, Firenze, G.Barbèra Editore, 1967.

31.Cf. p. 32r and p. 32v.of the “Introductory book”.

32.Cf. De humani corporis fabrica libri septem, Basel, 1543, V, chapter X: De renibus. pp.514-517.

33. Suffice it to read what he writes about uropoiesis: “the sub-stance of the kidneys drains the serous excrement through the venous and arterial capillaries that branch into it, thanks to its innate faculty and a well balanced temperament of its own”. No statement may be more “galenic”!!!

34.Cf. Observationes anatomicae (Venice, 1561), pp. 179-182.

35.Which I shall deal with below.

36. Cf. Humani corporis fabrica. etc., V, plate 21.

37. The three figures are placed vertically in the original plate.

38. Cf. mainly pp. 179-182.

39. Pietro Manna, the anatomist of Cremona to whom Fallop-pio dedicated his Observationes.

40.Cf. note n. 35.

41. Cf. Vesals Darstellung des Baues der Niere. in Archive für Geschichte der Medizin, VI (1913), 129-148 later added by R. Schmutzer in Sudhoffs Archive für Geschichte der Medizin und der Natuwissenschaften, XXVII (1934), 187-188.

42. As everyone knows, Eustachi had prepared all the copper plates for a complete anatomical treatise he had designed to write. His death prevented him from writing it and his copper-plates were lost till Giovanni Maria Lancisi succeeded in find-

Cite this article: Musitelli S. A Brief historical Survey of the Anatomophysiology of the Kidney. J J Nephro Urol. 2016, 3(1): 023.

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ing and published them (together with the plates concerning the kidneys, which had been already published by Eustachi himself) in Rome in 1714.

43.Cf. G. M. Lancisi’s letter to Giovanni Fantoni in the preface to the edition of Eustachi’s plates.

44. He also inserted the same figure in his Institutiones ana-tomicae (Anatomical education) , Theatrum anatomicum (An-atomical theatre) and Vivae imagnes (Living images).

45. Cf. Institutiones anatomicae corporis virilis et muliebris historiam exhibentes (Anatomical institutions that show the description of the male and female body) (4th edition, Basel, 1609)

46. Cf. Fig. 7.

47. Hypothesized by William Harvey in his Exercitatio ana-tomica de motu cords et sanguinis in animalibus (Anatomical practice on the movement of the heart and the blood in the animals) (Frankfurt am Main, 1628) and proven by Marcello Malpighi in the two Epistolae de Polonbius (Letters on the lungs) dedicated to his master Giovanni Alfonso Borelli (1608-1679) and printed in Bologna in 1661. Cf. L. Belloni , Malpighi, De pulmonibus, Per la Fondazione della Società Italiana di Iat-rochimica e i Congressi Nazionali di Anatomia e Medicina In-terna, Messina-Palermo, 1958.

48. Cf. VI, p. 2432. I quote Galileo’s passages from the National Edition of the works of Galileo Galilei (20 volumes edited by A, Favaro & I. Del Lungo), Barbera, Florence, 1890-1909.

49. “Philosophy” is “knowledge” and therefore “Science” to Galileo.

50. Cf. Il Saggiatore, VI, p. 347.

51. Suffice it to remember that to Marcus Aurelius Severinus (cf. note n. 20) “anatomy” does not derive from the Greek word “anà tomé” (dissection), but the Greek word “an átoma” (till the atoms)!

52. This physical phenomenon had been recently discovered by Bellini’s and Malpighi’s master Giovanni Alfonso Borelli (1608-1679).

53. It is worth observing that in the first part of his Execitato, in which he summarizes the theories of his predecessors, he ignored both Berengarius da Carpi and Bartlomeo Eustachi., although he surely knew at least Eustachi, whom he quotes in other works! The legitimate suspicion arises that he did not want to decrease the merits of his own discoveries.

54. Cf. figure 9 and figure 10.

55. The treatise is contained in Malpighi’s De viscerum struc-tura (Bologna, 1666).

56. The letter was anonymous, but the author was Giovanni Girolamo Sbaraglia (1641-1709), a merciless adversary of Mal-pighi.

57. In contrast with Bellini’s, who maintained that this tubule was rectilinear.

58. They are the first description of what – after the subse-quent and fundamental researches and discoveries – we call “nephron”.

59. The reader must have present that although Malpighi did not refuse some ideas of the “iatrochemistry” founded by Jo-han Baptist van Helmont (1577-1644), nonetheless he had not even the faintest idea of “chemistry” in the modern sense of the word. Cf. note n. 12. This lack of knowledge prevented him from giving a correct interpretation of this phenomenon.

60. Cf. fig. 14. This rather absurd theory was censured – al-though with no less absurd reasons – by Bellini’s and Mal-pighi’s master Giovanni Alfonso Borelli (1608-1679) and mainly by Paolo Mini (1642-1693), but confirmed by Malpighi in his Opera posthuma (1697).

61. He was one of Luigi Belloni’s schoolfellows. Cf. his “Il “De renibus” di Marcello Malpighi, in Physis, Rivista Nazionale di Storia della Scienza, VI, 4, 1964, Leo S. Olschkhi, Florence, p. 286 ff.

62.He never revealed which was the liquid !

63. The text wrongly reads “Bellinos” instead of “Bellinianos”

64. Cf. Thesaurus Anatomicus X, III, n. JXXXVI)

65. He followed the way paved by Paracelsus (1453-1521) and van Helmont (1577-1644)

66. Cf. his Mémoire pour servir à l’histoire des reins in “His-toire de l’Académie Royale des Sciences, année MDCC. Avec les Mémoires de Mathématique et de Physique, pour la même An-née, Tirés des Registres de cette Académie (Paris, 1748), pages 77-112 and plates V-VIII.

67. In concordance with Ruysch’s statement.

68. Cf. Sur la sructure des viscères nommée glanduleux, et par-ticulière sur celle des reins et du foi in Mémoire pour servir à l’histoire des reins in “Histoire de l’Académie Royale des Sci-ences, année MDCC. Avec les Mémoires de Mathématique et de Physique, pour la même Année, Tirés des Registres de cette Académie (Paris, 1753), pages 489-530 and plate XIV-CVI.

69. And Aristotle!

70. Against Aristotle’s statement that birds had not kidneys because of the missing of urinary bladder. Cf Galvani’s De re-nibus atque ureteribus avium (On the kidneys and ureters of the birds), in “De Bononiensi Scientiarum et Artium Instituto atque Academia Commentarii” (Commentaries of the Institute and the Academy of Sciences and Arts of Bologna), V/2, Bolo-gna, 1767, p.500 ff.

71. Cf. in particular “Lber decimus: de penitiori structura re-num” (Tenth book: On the deeper structure of the kidneys).

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72. Cf. “Müller’s Archiv für Anatomie, Physiologie und wissen-schaftlichen Medizin”, 1838, p. 103 ff. and Algemeine Anato-mie, Leipzig, p. 926, plate V, Fig. 18.

73. Devised by Charles Louis Chevallier (1804-1859) and Giovanni Battista Amici (1786-1868) respectively.

74.Cf. Bruno Zanobio, L’immagine filamentoso–reticolare nell’anatomia microscopica dal XVII al XIX secolo ( The fila-mentous-reticular image in the microscopic anatomy from the XVI to the XIX century), in Physis Rivista Nazionale di Storia della Scienza, III, 1960, Leo S. Olschkhi, Florence, p. 299 ff.

75. Cf. W. Bwmann, On the Structure and use of the Malpighian Bodies of the Kidney, with Observations on the circulation through that Gland in “Philosophical Transactions of the Roy-al Society of London”, 1842, I, p. 57 ff,. Cf also F. Grondona, La strutturistica del rene da F. Ruysch a W. Bowmann (The renal

Jacobs Publishers 20structure from F. Ruysch to W. Bowmann) in Physis, Rivista Nazionale di Storia della Scienza, VI, 5, 1965, Leo S. Olschkhi, Florence, p.281 ff.

76. Cf. Sur un nouveau procédé d’injection, anatomiques – Ex-trait d’une note de M. Doyère, in “Comptes Rendus hebdom-adaires des séance de l’Académie des Sciences”, 13 (1841), p. 75 ff.

77. It consists of a first injection of a saturated potassium dichromate solution followed by an injection of lead acetate solution into the vessels.

78. Cf. On the structure, etc. p. 62 ff.

79. Cf. La strutturistica del rene da F. Ruysch a W. Bowmann quoted above (cf. note n. 74), p. 315.