E. A. (Edward Albert) Sharpey-Schäfer.

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of the latter essential constituent of the body-fluids which makes the
consumption of common salt with the food a necessity in all cases
where the diet is rich in potassium.^

Calcium and magnesium. — In human urine, about 0"2 to 0"4 grms.
of lime (CaO) is excreted per diem.

Of the lirne salts present in the food, only a small proportion is
excreted by the urine. Much of the lime remains in an insoluble form,
and is not absorbed at all, while of that which does enter the circulation

1 Cf. Salkowski and Leube, " Lehre vom Havn," 1882, S. I7i, 464, 465 ; see also Kast,
Ztsdir. f. pliysiol. Clunn., Strassbiirg, 1888, Bd. xii. S. 271.

2 Wiirster and Schmidt, CentrcdU. f. PJu/sioL, Leipzif? u. AVien, 1887, Bd. i. S. 421.

3 Cf. Salkowski, FircJww's ArcJdv, 1871, Bd. liii. S. 209 ; Munk, Berl. Idin, JKrJinscJir.,
1887, S. 432.

^ Bunge, "Lelirliucli dor idiysiol. Chem."


a considerable fraction is re-excretecl into the lower bowel.^ The
administration of dilute mineral acids, which decomposes to some extent
the insoluble phosphates of the food, increases the urinary lime salts,
and, conversely, when sodium phosphate is taken in large quantities, the
lime may almost disappear from the urine.

Very interesting is the observation of G. Hoppe-Seyler,^ who found
that the excretion of lime salts by the kidneys is much greater during
conditions of rest than during exercise, a fact which doubtless depends,
in part at least, upon the effect of exercise on the excretion into the

As a general rule, the urine contains about twice as much magnesia
as lime.^ Most food-stuffs, other than milk and eggs, contain more
magnesium than calcium salts. The phosphates of the former are also
more soluble, and as both bases are largely present as phosphates in the
food, it is to be understood that more magnesium will be absorbed and
excreted. When, as during starvation, the ingestion of magnesium salts
ceases, the lime is found to be in the greater proportion.

The presence of calcium in urine is easily demonstrated, and its amount
determined by acidifying the fluid with acetic acid, and adding ammonium
oxalate, when all the hme separates as the insoluble crystal hne calcium oxalate,
which may be filtered off and weighed as calcium carbonate, into which it
is converted on gentle ignition. In the filtrate from this, the magnesium is
precipitated as triple phosphate upon the addition of ammonium chloride,
ammonia, and, if necessary, of some extraneous alkaline phosphate.

Iron. — The urine contains, as a rule, a very minute quantity of iron,
and frequently no detectable trace. It has been found increased in
diseases, such as pernicious anfemia, but never rises to more than a few
milligrammes in the twenty-four hours. It is a remarkable fact that
this metal, if present at all, is, to a large extent, precipitated in association
with the pigmented crystals of uric acid, which separate when the urine
is acidified with hydrochloric acid. It may be detected in the ash of
large quantities of the urine, by taking a solution of this to dryness with
a little nitric acid, dissolving the residue in water, and testing with
potassium sulphocyanide, which gives with ferric salts a blood red

G-ENEEAL Characteristics of the Urinary Excretives.

It might perhaps be expected that the waste products of meta-
bolism, on leaving the body, would in general represent the simplest
compounds of physiological chemistry, and would stand farthest of all
removed from the complexity of the tissue proteids. That this is not
entirely the case, however, will have been clear from the facts set forth
in previous sections ; it is, indeed, striking to observe how many of the
organic excretives arise by synthetic processes from simpler precursors
in the body.

There is one form of chemical change which takes an important and

1 Voit, Ztschr. f. Biol., Milnclien, 1892, Bd. xi. S. 387-397, where other references
will be found.

" Ztsdir. f. pliysiiol. Chem., Strassburg, 1891, Bd. xv. S. 161.

^ Most analyses bear out this statement, but those of Bunge, given on p. .573, show an
excess of lime.


even dominant share in the processes of constructive metabolism : that,
namely, of dehydrolysis — the synthesis of larger molecules by a con-
jugation of smaller, associated with elimination of the elements of
water. This process is known to chemists as one of " condensation."
In destructive metabolism, on the other hand, the converse process
of hydrolysis is an important factor.

While of most obvious importance in the physiology of plants,
in which constructive metabolism starts from a lower chemical level,
" condensation " is also prominent in all constructive processes of which
we have any accurate knowledge in the animal organism. Being thus
in general so characteristic of assimilative processes, it is remarkable
how frequently dehydrolytic synthesis interrupts the course of meta-
bolic breakdown and reappears as a final step before excretion.

We have dealt with a typical instance of this in the formation of
hippuric acid from benzoic acid and glycine in the kidney, and we have
seen that a like process occm-s in the production of ethereal sulphates,
and the conjugate compounds of glycuronic acid. We may note, too,
that many substances introduced experimentally into the body undergo
kindred conjugations before excretion.

The theory of the origin of uric acid and the alloxuric bases from
nucleins, does not perhaps predicate any synthetic step in the produc-
tion of this group of excretives ; but however far-reaching may be the
truth of this theory, it must be admitted that there is much reason for
ascribing the origin of at least some fraction of these substances, as
found in the urine, to conjugative processes in the liver and kidney. In
birds there can be little doubt that uric acid arises by a synthetic

In the most important of the chemical changes antecedent to
excretion — the formation of urea from ammonium carbonate in the
mammalian liver — we have a process which I venture to think belongs
essentially to the same chemical picture. Though not resulting, properly
speaking, in a synthesis, the dehydrolysis which here occurs is a chemical
change against the line of least resistance, and suggests an influence of
the same type as that producing the synthetic results just discussed.
Without misuse of the vague and somewhat discredited terms " organic "
and " morganic, we are entitled to look upon the dehydrolysis of am-
monium carbonate as a return from the latter to the former category ;
the excretive stands physiologically on a higher level than its precursor.

To complete whatever of suggestion these considerations may contain,
we may note finally the dehydrolysis which creatin suffers before ex-
cretion as creatinin. Even here we meet with a change which, for the
conditions under which it occurs, is one from a more stable to a less
stable substance.

It would seem that just before excretion there occurs an arrest of
the normal processes of down-grade metabolism (in which hydrolysis
goes hand in hand with oxidation, resulting in a series of compounds of
increasing stability), and a brief return to dehydrolysis and to the type
of constructive processes. It is at any rate interesting to observe that
the renal excretives are as a class more complex or less stable than
their immediate precursors in the body. When the urine decomposes,
under the destructive influence of enzymes derived from micro-
organisms, many of the precursors reappear ; the urea again becomes
ammonium carbonate ; hippuric acid and its analogues give place to


bcuzoic acid, creatinin may again take up water, and uiic acid is
rapidly hydrolysed.

The urinary nitrogen, it will have been observed, always appears
either as ammonia (NH^), or more typically in compounds containing
the derived amiclo ( - NHg) or imiclo ( -= NH) groups. Compounds con-
taining the other fundamental form of organic nitrogen, the cyanogen
type ( - C = N, or - N = C), are represented only by the minute
quantity of potassium sulphocyanide, which is in all probability directly
derived from the saliva. Although a small proportion of the nitrogen
is excreted in aromatic compounds, it is never, in human urine, present
in the benzene nucleus of these, but always in side chains or accessory
atomic groups within the molecule.

The carbon ring of the benzene nucleus is especially resistant to
oxidation in the body, the open chain of carbon atoms, proper to
substances of the fatty series, being much less so ; and for the most
part we find that the normal renal excretives do not reach such
molecular size as to contain as many as six carbon atoms, unless they
contain the aromatic nucleus. As illustrating the degree of molecular
complexity found in the organic urinary compounds, we may remember
that the molecular weight of urea is 60, that of creatinin is 113,
of uric acid 168, and of hippuric acid 181. The intact renal
epithelium, it is true, passes substances, such as the pigments, the
molecular weight of which is much greater than the above, but only
in small quantities.


In mannnals, amphibia, fishes, and in certain molluscs, urea is the
chief end-product of nitrogenous metabolism. In birds, reptiles, and
arthropods, on the other hand, the nitrogen is excreted mainly in the
form of uric acid. In spiders and in some few other groups of inverte-
brates, the chief excretive has been shown to be guanin.

A study of the renal function, from a comparative point of view,
offers one aspect of great interest and some difficulty, to which Sir
William Eoberts has called attention. It is remarkable that the wide
differences in the nature of the renal excretion in mammals and the
Sauropsida respectively, should yet be associated with almost complete
identity in the anatomical structure of the kidney. The kidney of
the bird has a glomerular mechanism identical with that of the
mammalian organ, and the same tubular arrangement of a secretory
epithelium ; and yet practically the sole function of the organ of the
bird, in contrast to the remarkably complex duties performed by that of
the mammal, is to secrete quadriurates. " The chlorides, phosphates, and
sulphates, the lime and magnesia salts, the pigments and the large
volume of water — all of which figure as prominent and even essential
components of mammalian urine — are either wholly absent from the
urine of birds and serpents, or are only present in such minute traces
as might be derived from the lubricating mucus and epithelial debris
with which the secretion is incidentally admixed " (Eoberts).

The physiological differentiation, whereby soluble urea takes the
place of insoluble uric acid, in accordance with the needs of an
organism excreting a liquid urine, is now known to occur quite at the
final stages of metabolism. It is almost certain that, in the main, the


waste products which leave the tissues are the same in birds and
mammals. In the liver of the former these products are prepared for
excretion by a change into the form of uric acid, while in the latter
the hepatic influence produces urea. There is a great preponderance of
experimental evidence to show that when uric acid is administered to
mammals it is converted into urea before excretion, and that when urea
is given to birds the converse change occurs. The contention of Haig,
that when uric acid is taken by the mouth (in man) it is excreted
unchanged, is not supported by other observers.

As to the small quantity of uric acid found, nevertheless, in the
urine of mammals, if we accept the theory of its exclusive origin from
nucleins, it is clear that we cannot look upon it as in any sense
physiologically akin to the main part of the normal excretion of birds,
for this must represent the waste nitrogen of the tissues as a whole.
But this theory apari, the view is plausible, and indeed it cannot be said
to be yet disproved, that we have in the mammalian uric acid a vestigial
relic of the earlier type of excretion — ■" something analogous with the
vermiform appendix, the ductus arteriosus, or the ear-point." The
actual proportion present in the urine of different mammals is very
variable. In most animals the relative amount is less than in man, but,
except occasionally in the cases of the cat and dog, it has never been
found to be absent. The presence of the small amount of uric acid in
the urine of mammals is paralleled by the existence of minute quantities
of urea in that of birds and reptiles.

Creatinin has been found wherever looked for in the urine of various
species of mammals, but is said to be absent from the excretion of birds.

Hippuric acid is represented in birds by the analogous compound,
ornithuric acid, which is a condensation product of benzoic acid with
diamidovalerianic acid. An aromatic acid, apparently peculiar to the
urine of dogs, is known as kynurenic acid, and has the composition of
an oxychinolin-carboxylic acid (OH.CjH^N.COOH).

The large proportion of hippuric acid in, and the absence of
ammonium salts from, herbivorous urine, have been shown in previous
sections to be, in common with the alkaline reaction of the fluid and
its richness in salts, a direct effect of diet.

Of the urinary pigments in the lower animals we have no accurate

It is impossible at present, owing to the wide gaps in our knowledge,
to take any broad view of the comparative chemistry of the urine. A
series of analyses are much needed, from the results of which we could
form some judgment as to the line of evolution which has led from
the simple renal excretions of the invertebrates to that most complex
of physiological fluids — mammalian urine.'^

^ See ou the subject of the comparative chemistry of the urine, Rywosch, Wicn. mcd.
Wchnschr., 1893, Nos. 47 and 48.


By Eknest H. Starling.

Contents. — Theories of Urinary Secretion, p. 639 — Theory of Bowman, p. 639 —
Theory of Ludwig, p. 640 — Secretion of Water, p. 641 — Methods, p. 642 —
The Concentration of the Urine, p. 650 — Heidenhain's Criticism of the Theory
of Ludwig, p. 652 — Experiments of Nussbaum, p. 655 — Experiments of Ribbert,
p. 656 — Experiments of Bradford, p. 656 — The Inliuence of the Nervous
System on the Secretion of Urine, p. 659.

Theories of Urinary Secretion.

In all the organs of the body whose functions have been investigated by
physiologists, it has been found that a difference of function is invariably
associated with a difference in structure, so that the interdependence
of function and structure has become an axiom. We are therefore
justified in founding theories concerning the physiological function of
an organ on a purely anatomical study of its structure, although the
complete establishment of such theories must ultimately be afforded
by physiological investigations.

The kidney differs from all other secretory glands, in the fact that
at the blind end of its tubulus we find a structure — the glomerulus —
where the vascular capillaries abut directly on the lumen of the tubulus,
without the interposition of any lymph space. Ever since the publication
of Bowman's paper on the Malpighian bodies of the kidney, these have
been looked upon as the essential source of the watery constituents of
the urine.

Theory of Bowman.— Bowman,^ who founded his theory of urinary
formation exclusively on the anatomical structure of the kidney in
various animals, concluded that "as the tubes and their plexus of
capillaries were probably the parts concerned in the secretion of that
portion of the urine to which its characteristic properties are due (the
urea, lithic acid, etc.), the Malpighian bodies might be an apparatus
destined to separate from the blood the watery portion."

The following are the grounds on which Bowman based this
hypothesis : —

{a) That the titbes are secretory.

(1) The extent of surface obtained by the involutions of the


(2) The fact that the lining memlirane of the tubules is formed

by thick epithelial cells, similar to those found on the
secreting surface of all true glands.

'^PMl. Trans., London, 1S42, p. 57.


(3) The capillary network suiTounding the uiiniferous tubes is

the counterpart of that investing the tubes of the testis,

allowance being made for the difference in the capacity of

these canals in the two glands.

(6) That the Malpighian bodies differ from the secreting iKirts of

true glands.

(1) The Malpighian bodies comprise but a small part of the

inner surface of each kidney, there being but one to each
tortuous tube.

(2) The epithelium immediately changes its characters as the

tube expands to embrace the tuft of vessels.

(3) The blood vessels, instead of being on the deep surface of

the membrane, " pass through it and form a tuft on its
free surface."

(4) The peculiar arrangement of the vessels in the Malpighian

tufts is clearly designed' to produce a retardation of the
blood through them, while the orifice of the tubule is
encu'cled by ciha in active motion directing a current
towards the tubule, so tending to remove pressure from
the free surface of the vessels and to encourage the escape
of their more fluid contents. " Why is so wonderful an
apparatus placed at the extremity of each uriniferous
tube, if not to furnish water to aid in the separation and
solution of the urinous products from the epithelium of
the tube ? "
The appearance of this paper fell at a time when, led by Ludwig,
Helmholtz, and du Bois Eeymond, physiologists were endeavouring to
replace the misty " vitalistic " conceptions which had until then prevailed,
by an accurate comparison of vital phenomena with their physical or
chemical counterparts, and seeking to estabhsh physiology as an exact
experimental science on a par with physics. It was impossible, therefore,
that the views of Bowman, devoid as they were of experimental founda-
tion, should remain unchallenged.

Theory of Ludwig. — In 1844, Ludwig^ put forward his well-known
mechanical theory, for the establishment and testing of which a large
volume of work has been done, the greater part under the direction of
Ludwig himself. According to this theory, all the energy for the secretion
of urine is ultimately derived from the heart-beat. In consequence of
the high pressure obtaining in the capillaries of the glomeruli, a fluid
is filtered through, containing all the constituents of the urine in very
dilute solution. This dilute solution jjasses down the tubules, and in its
passage undergoes changes, in consequence of diffusion between it and
the fluid (lyniY^h) surrounding the tubules. Since water will always
pass from a dilute to a more concentrated fluid, and since the glomerular
filtrate is, according to the theory, poorer in solid constituents than
the serum, water will pass from urine to lymph, and the urine will
become more concentrated until it acquires the normal characters of

In this theory of Ludwig there are three distinct jiropositions to be
investigated. These are —

1. That the secretion of water is a purely mechanical process,

1 Wagner's " Handwiiiterbucli, " 1844, Bd. ii. S. 637; " Lclirbuch der Physiologic,'
Aull. 2, iSfjS, Bd. ii. S. 373.



depending only on the blood pressure in the glomerular capillaries
and the permeability of the filtering membrane.

2. That this dilute urine is concentrated in the tubules by giving up
its water to the surrounding lymph, in consequence of differences of
concentration between the glomerular filtrate and the lymph.

3. That all the urinary constituents are turned out of the blood
through the glomeruli {i.e. with the water) in dilute solution.

In discussing the experimental data bearing on these propositions,
we shall find that only in the first part of the theory are the
experimental facts consonant with Ludwig's hypothesis, and that it is
impossible to explain the formation of normal urine without assuming
the active intervention {i.e. the performance of work) by certain of the
living elements of the kidney in the process. In this case, as in so
many others in physiology, the " how " of the cellular activity is
at present absolutely unknown to us, although we may confidently
expect, with the advance of the science, to be able to trace the
manner in which the cell utilises the energy of its food for this special

Secretion of water. — One of the strongest facts in favour of Ludwig's
hypothesis is the indubitable
connection which exists be-
tween the circulation through
the kidney and the amount
of urine, i.e. of water, secreted.
It is evident that a mechanical
filtration or separation of the
watery and crystalloid consti-
tuents of the blood in the
glomeruli must depend on two
factors —

1. The difference of pres-
sure between the blood in the
glomerular capillaries and the
urine in Bowman's capsule.
Since under normal circum-
stances there is a free outflow
of urine from the capsule by
means of the tubules, we may
regard its pressure as practi-
cally nil, so that the only
changeable factor in the pro-
cess will be the blood pressure
in the capillaries.

2. The rapidity of the blood flow through the glomeruli must also
have some influence on the filtration, as this process will go on the
more readily the more often the fluid presented to the filter is renewed.
As a rule, the changes that raise the pressure in the capillaries also
increase the velocity of the blood through them, so that it becomes
difficult to dissociate the part played by each factor in influencing the
urinary secretion.

If we consider the manner in which changes in the glomerular
circulation are brought about, we see that it may be affected by changes
either in the general blood pressure or in the calibre of the smaller
VOL. I. — 41

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\ ;;:'>,i,,,;


1 ■ "




...^!- -■

. .'<sii'^-


^^, I.





Fig. 59.

-Roy's oncometer. (For explanation of
lettering, see next figure.)



arteries. The pressure in the glomerular capillaries will be raised and
the velocity of the blood increased —

1. By a rise of general blood pressure. This may be due to —
(a) Increased force or frequency of the heart beat ;

(&) Constriction of vascular areas in other parts of the body.

2. By dilatation of the renal arterioles, the general blood j^ressure
remaining constant.

3. By obstruction of the renal vein. In this case the velocity will
be diminished.

F:g. 60. — Diagrammatic section through Roy's oncometer, to show position
of kidney. A, outer, and B, inner, brass capsules. These are fixed
together by the screw C. G, the kidney. D, a clamp for fastening
the two halves together after the kidney has been inserted. K, renal
vessels and ureter.

The pressure and velocity in the glomerular capillaries will be
diminished —

1. By diminished general blood pressure, which may arise from
a weakening or slowing of the heart-beat, or from dilatation of vascular
areas in other parts of the body.

2. By constriction of the vessels in the kidney itself.

Methods. — In the earHer researches^ on the connection between the
renal circulation and the flow of the urine, the observers had to content them-

^Max Hermann, Sitzungsh. d. k. ATcad. d. Wissensch., Wien, 1859, Bd. xxxvi. S. 349 ;
3 861, Bd. xlv. S. 317 ; Ustimowitsch, Arh. a. d. 2'>hys!oL And. zii Lcijjziff, 1870.



selves with a measurement of the general blood pressure, and could only
obtain direct evidence as to the local changes in the renal circulation by
inspection of the kidney. It was not until the ingenious application of
plethysmographic methods to the kidney in situ, by Roy/ that we could
obtain a precise and quantitative estimate of the changes produced on the
circulation through this organ by the measures employed by the older observers.
Eoy's instrument for registering changes in the volume of the kidney
consists of two parts, in one of which, the oncometer, the kidney is placed,
while another, called the oncograph, serves as the recording part of the
apparatus. The oncometer consists of two halves hinged together, each of

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 90 of 147)