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and will be discussed in another section of this volume. The former
result (the hydruria) may, however, be analogous to the results of
Eibbert's experiments, and may be due to a diminution in the actively
absorbing or secretory mechanisms of the kidney, i.e. the convoluted
tubules. It seems probable that a deficiency in the excretory powers of
the organism could be more easily compensated by augmenting the
glomerular transudation by means of the blood supply to the glomeruli,
than by increasing the work of the cells of the convoluted tubules.

Arguments based upon the reactioii of urine. — An objection which has
been frequently urged against the filtration liypothesis is that, whereas
the blood serum or plasma is in all animals alkaline, the urine, except in
those cases where there is a rich supply of alkali in the food, is acid
in reaction. It seems difficult to conceive how a process of filtration
could effect this change in the reaction of the filtrate. Since all author-
ities are agreed that the urine undergoes changes in composition on its
way through the tubules, it becomes important to find out whether the
urine, as it is formed by the glomeruli, is alkaline or acid.

Dreser^ has sought to determine this question by examining the
microchemical reactions in the different parts of the kidney in the frog.
As his indicator he used acid fuchsin (rubin S.) This substance is a
brilliant red in acid solutions, bvit is almost colourless in weak alkaline
solutions. It is, therefore, a convenient substance to use in order to
demonstrate the formation of acid in muscle during tetanus. A strong
solution of this dye was injected into the dorsal lymph sac of the frog.
An hour or two later the urine that was secreted was of a deep red
colour, and was acid in reaction. On examining the kidneys, the dorsal
part in which the glomeruli are situated was found to be colourless, but
the tubules in the ventral part were filled with red secretion. If the
injection were repeated the red coloration extended to the lining cells
of the tubules. From his experiments with this and other dyes, Dreser
concludes that the production of the acid reaction is effected by the cells
•of the convoluted tubules, and that the glomerular transudate is alkaline.

This conclusion is borne out by the results of injecting any kind of
■diuretic. If the glomerular transudate is alkaline, and is also rendered
acid in its passage through the tubules, we should expect that the more
abundant the glomerular transudate, the shorter would be the time taken
in its passage through the tubules, so that the urine pouring into the
bladder would tend to approximate in reaction and composition the
original glomerular transudate. Such is found to be the case. Whatever
means we use to induce profuse diuresis, whether by the injection or
administration of drugs such as caffein or theobromin, or the adminis-
tration of saline diuretics, or the production of hydrtemic plethora,
we find that the acid reaction of the urine disappears, to be replaced by
a neutral or alkaline reaction. We may conclude, with a high degree of
probability, that the glomerular part of the urinary secretion is alkaline
in reaction, and that the acid reaction of the urine of carnivora or
of starving herbivora is due to the changes wrought on the glomerular
transudate by the cells of the convoluted tubules. Whether this
change is due to the secretion of acid salts, or to the absorption of
alkaline salts by the cells of the tubules, we are not in a position to

1 Ztschr.f. Biol, Mlincheu, 1885, Bd. xxi. S. 41.
VOL. I. — 42


An ingenious attempt has been made by Liebermann^ to explain the
chemical mechanism by Avhich the cells of the tubules effect this change in
reaction. This author has described a class of bodies which may be extracted
from the mucous membrane of the stomach or from the kidney, and which
consist of compounds of lecithin and proteid. These he designates lecith-
albumins. These substances are acid in nature, and are capable of combining
with alkalies. Liebermann imagines that, as the alkaline salts of the blood
plasma pass through the epithelial cells of the kidney, they are split up by these
acid insoluble lecith-albumins, which combine with a portion of the bases, so
that the remainder of the fluid which reaches the lumen of the tubule contains
acid salts or free acid. Of course this process would come to an end as soon as
the acid affinities of the lecith-albumins in the cells were satisfied, and in this
way one might explain the speedy appearance of an alkaline reaction when
large quantities of urine are secreted. Under normal circumstances, however,
Liebermann assumes that the carbon dioxide, which is the normal product of
tissue metabolism in the kidney, splits up the compound formed in the cells
into free lecith-albumin and alkaline carbonates, these latter being then
removed by the venous blood stream. As supporting evidence for this hypo-
thesis, Liebermann states that the kidney tissue, like lecith-albumin itself, if
treated Avith soda solution, and then washed repeatedly with water to remove
excess of the latter, becomes strongly alkaline. If now the alkaline tissue be
suspended in water, through which a stream of CO^ is passed, and be then
again washed thoroughly, it will be found to be strongly acid, having given up
all its soda to the carbon dioxide.

Conclusions. — It is e^adent that the experimental facts at our pre-
sent disposal do not allow of a definite decision as to the exact manner
in which the secretion of urine is effected. It will be convenient,
therefore, to summarise the two modes of interpretation, either of which
may be applied to the known facts.

According to the Bowman-Heidenhain hypothesis, the secretion of
urine is due to the activity of two sets of cells. The flattened epithelial
cells covering the glomeruli take up from the blood, circulating through
the glomerular capillaries, water and salts, and transfer these substances
to the l^egiuning of the urinary tuluile. Their activity is chiefly depend-
ent on the activity of the blood flow through the capillaries. But they
may be also excited to active secretion by the presence of certain of the
urinary constituents in the blood, such as water and salts, or possibly by
diuretics, such as caffein. On the other hand, the rodded cells, lining the
convoluted tubules and the ascending loop of Henle, secrete specific
urinary constituents, such as urea and uric acid, together with a certain
amount of water. They also secrete certain abnormal constituents of the
blood, such as indigo -carmine. Their activity is chiefly determined by
the amount of urea or uric acid in the blood.

If, on the other hand, we accept Ludwig's hypothesis, we must
introduce into it certain modifications, necessitated by later inquiries,
and assume that in the secretion of urine, as in so many other of the
bodily functions, there is a mixture of what we may term physical and
physiological processes. It seems probable that in the glomeruli the
process is largely if not exclusively physical ; that is to say, we have here
a transudation of the watery and crystalloid constituents (including
urea) of the jjlood plasma. The extent and nature of this transudation
are determined —

1. By the pressure in the glomerular capillaries.

^ Arch. f. d. ges. Physiol., Bomi, 1894, Bd. liv. S. 585.


2. By the velocity of flow tlirougii the capillaries.

3. By the permeability of the capillary wall and the glomerular

This watery transudate is concentrated and altered on its way through
the tubules, in consequence of the al:)Sorption of water, and probably of
certain of its crystalloid constituents. This absorption must be due to
the active intervention of the cells, since the osmotic pressure of the
urine is considerably higher than that of the blood pressure. Diuretics
may act in two ways. The saline diuretics increase the pressure and
velocity of the blood in the glomerular capillaries, not only by increasing-
the volume of the circulating fluid, but also probably by a direct dilator
action on the afferent vessels of the glomeruli. A similar local dilator
effect is produced by drugs such as caffein or theobromin ; but in these
cases the drugs probably exert a paralysing influence on the absorbing
mechanism of the kidney, i.e. the cells of the convoluted tubules, so that
the glomerular transudate may undergo little change on its way to the
ureter and Ijladder.

One of the strongest arguments in favour of this modified Ludwig hypo-
thesis is the fact that the more we augment the flow of urine, whether by
caffein, sahne diuretics, or production of hydraemic plethora, the more nearly
does its osmotic pressure, saline constitution, and reaction approximate that of
the blood plasma. It would seem that in the glomeruli we have an apparatus
which, like the capillaries of the abdominal viscera but in a still higher degree,
reacts to changes in the intracapillary pressure, and so serves to regulate
accurately the amount of fluid circulating in the blood vessels.

Whether we look upon the cells of the convoluted tubules as secre-
tory or absorptive in function, we have at present no evidence that the
cellular covering of the glomeruli acts otherwise than passively in the
production of the glomerular part of the secretion. It must be remem-
bered, however, that under certain circumstances, as after ingestion of large
quantities of fluid, the osmotic pressure of the urine may fall below that
of the blood plasma. Dreser ^ interprets this as pointing to an activity
of the glomerular epithelium. I have shown above that it may equally
well be explained l^y assuming an absorption of salts by the water-logged
tubule cells, or an active excretion of water by these cells. I may
mention here that I. Munk and Senator,^ as a result of researches carried
out for the most part on the excised kidney, have come to a conclusion
analogous to that just stated, namely, that in the production of urine we
have a co-operation of physical and physiological factors. According to
these authors, water and part of the urinary salts (especially NaCl)
are transuded through the glomeruli in direct consequence of the blood
pressure, i.e. by a process of filtration, although the rapidity of the blood
flow is at least of equal importance with its pressure. The specific
urinary constituents — urea, uric acid, hippimc acid, etc., together with
another portion of the urinary salts (NaCl, sulphates and phosphates)
— are secreted by the active intervention of the cells of the tubules,
especially the convoluted tubules. These substances are secreted in a
dissolved condition, and must, therefore, take a certain amount of water
with them.

The influence of the nervous system on the secretion of urine.
— The discovery by Berkeley ^ of a distribution of nerve-endings to the

^ Loc. cit. - Virchoiu's ArcMv, 1888, Bd. cxiv. S. 1. ^ Loc. cit.


tubules of the kidney suggests that in this organ, as in the salivary
glands, the secretion of urine may be under the dii-ect control of the
central nervous system, apart from any influence that this system may
have on the renal circulation. We have already seen that the urinary
secretion is extremely susceptilile to variations in the pressure and
velocity of the blood in the renal vessels, and also that these latter are
under the direct control of the nervous system by means of vaso-dilator
and vaso-constrictor nerve fibres.

Various authorities have descriljed experiments which should
demonstrate the existence of secreto-motor nerves to the kidney. Thus,
in 1835, Claude Bernard^ showed that in some cases, where puncture of
the medulla was carried out with the view of producing diabetes, the
result was an increased flow of urine, containing no sugar, i.e. diabetes
insipidus. These experiments were repeated in much greater detail by
Eckhard,^ who showed that, in the rabbit, polyuria might be caused, not
only by a puncture of the medulla, but also by chemical or mechanical
stimulation of the neighbouring portion of the superior vermis of the
cerebellum, especially if, previously to the operation, the nerves going
to the hver had been divided. Moreover, it is a familiar fact to
clinicians, that injuries to the head, epileptic attacks, and especially
lesions in the neighbourhood of the medulla, may bring about a condi-
tion of diabetes insipidus.

We know already that division of one splanchnic nerve will cause
an increased secretion of urine in the kidney of the same side, and it is
natural to imagine that the mechanism of the increased urinary sec-
tion after the fiqiiTe is of the same nature. Eckhard pointed out, how-
ever, that the course of events is different in the two cases. After division
of one splanchnic, the flow of urine is almost immediately somewhat
increased, and this moderate increase lasts a considerable time (three to
four hours at least). The first result of puncture of the medulla is a
cessation of the urinary flow. This is followed shortly by an increase
much greater than is caused by section of the splanchnic, ' but only
lasting one to two hours. Moreover, the effect of the diabetic puncture
is observaljle even after section of the splanchnics, as well as of all the
nerves which may possibly send branches to the kidney. Eckhard con-
cludes, therefore, that the effect must l:)e due to one of two causes :
either an increased general blood pressure, in consequence of the
stimulus caused by the puncture, or the excitation of nerve fibres which
run in the walls of the renal artery itself. The first explanation must
be rejected, since direct measurement of the blood pressure does not
show any definite rise in consequence of the puncture. We must there-
fore accept the second explanation as the correct one. Eckhard regards
these nerve filjres as secreto-motor, and belie\'es that the urinary secre-
tion is under the control of a nerve centre, situated most probably in
the medulla. He bases this hypothesis on the facts that section of the
cord below the medulla stops the flow of urine, and that stimulation of
the cut cord does not bring back the flow, in spite of the rise of blood
pressure which is induced. We know now, however, that the negative
result of stimulating the cut cord is due to the constriction of the renal
vessels, which occurs together with those of other parts of the Ijody, so

^ "Lefons de physio].," 1835, tome i. p. 339.

'- Beitr. z. Anat. u. Physiol. {Eckhard), Giessen, 1869, Bd. iv. S. 1-32 :iud 1.^3-193;
1870, Bd. V. S. 147-178 ; 1872, Bd. vi. S. 1-18 and .51-94.


tliat the increased general blood pressure is powerless to send more
blood through or to raise the pressure in the renal capillaries.

The facts can be equally well explained if we assume that these
hidden nerve fibres are vaso-dilator in function — an assumption which
would be in accord with the numerous other facts we have learnt with
regard to the regulation of the urinary flow by the central nervous
system. We may conclude, therefore, that the existence of secretory
nerves to the kidney is not proved, the subjection of the renal secretion
to nervous influences being effected exclusively through the intermedia-
tion of the vascular nerves.

As an additional argument against the dependence of renal secretion
on the nervous system, Heidenhain quotes a number of experiments
made by Bidder ^ on frogs, in which the secretion of urine continued
normally, although in some animals the whole spinal cord, in others the
whole nervous system, with the exception of the medulla, had been

'^ Arch. f. Anat. u. Physiol., Leipzig, 1844, S. 376.



CoxTEXTS : — General Cousideratioiis, p. 662 — Influence of the Nervous System, p. 663
— Action of Pilocarpine and Atrojjine, p. 664 — Influence of Diet, p. 664 —
Place of Formation of tlie Organic Constituents, p. 665 — Manner in which the
Secreted Materials j^ass out of the Cells, j). 665 — Mechanism of the Discharge
of Milk, p. 667.

The compositiou of milk has been dealt with in a previous article
(pp. 125 to 140). Here it may therefore be simply noted, with regard
to its organic constituents, that these are remarkable in being peculiar
to the milk, not occurring in any of the other secretions or tissues of the
body (cf. however, footnote 1, p. 665), nor in foods which have not been
]3repared from milk. The mammary gland-cells, therefore, unquestionably
form the products of secretion themselves from materials derived
through the lymph from the blood, and cannot be regarded, except as
concerns some of the inorganic substances, as acting merely as filtering
agents for allowing the passage of materials in solution from the blood.
And even with regard to the inorganic substances,^ the proportion of
these is so different from that in which they occur in the blood and
lymph, that no filtration hypothesis appears in any way tenable even for
these. The gland-cells are further peculiar in that they only, as a rule,
function actively for a certain period after parturition, being at all
other times entirely inactive, although capable occasionally — it is said
even in the male — of being excited to activity by stimulation of the
nipple by a sucking action, such as that performed by an infant. Prior
to, and during such periods of activity, the whole gland becomes greatly
enlarged, l^oth by an increase in size of existing alveoli, and also, perhaps,
by a sprouting out of new alveoli. The cells lining the alveoli become
enlarged, and probably also multiply, for they are said to show evidence
of karyokinesis.

The alveolar cells begin to accumulate within them granules,
partly of a proteid, partly of a fatty nature (although the latter may
more fitly be described as globules), and the alveoli get filled, before
there is any call for the pouring out of the secretion, with a clear fluid
(coagulating to a finely granular material in pieces of the gland thrown
into alcohol), which contains a few fatty globules of different sizes, and here
and there cells filled with granules, staining with osmic acid, and appar-
ently identical with the colostrum corpuscles which are found in the milk of

^ Bunge has shown that, Avith the exception of iron, the inorganic substances of milk
occur in neai'ly the same proportion as in the ash of uew-Lorn animals ("Text-Book," Woold-
ridge's translation, p. 107).


the first two or three days after parturition, and which are sometimes
even to be detected during full lactation. These colostrum corpuscles are
seen to be amoeboid when examined on the warm stage, and are, there is
little doubt, leucocytes which have wandered out from the interstitial
connective tissue of the gland into the lumen of tlie alveoli. Some have
regarded them as detached epithelial cells, and look upon their presence
in the alveoli and in the milk as evidence of the normal occurrence of
such detachment during active secretion (see p. 666) ; but it must be
admitted that they have neither the appearance of epithelial cells, nor
do the latter tend to exhibit any such amoeboid movement as is shown
by the colostrum corpuscles. These corpuscles, in fact, seem to be
rather analogous to the salivary corpuscles (see p. 344), and to be
similarly derived from emigrated leucocytes.

During the period of lactation the alveoli secrete milk, not only
whilst the gland is being drawn by the process of sucking or milking,
but in the intervals of such processes, so that the milk accumulates
both in the alveoli and in the ducts. The latter are provided with (in
some animals very considerable) dilatations, which serve as reservoirs
for the accumulated secretion, and it is mainly this accumulated milk
which is poured out during the milking. No doubt fresh milk becomes
secreted to take the place of that which is drawn away ; and as a con-
comitant to this fresh secretion, there is a considerable flush of. blood to
the gland. It has been calculated that the udders of a cow could not
contain all the milk which is sometimes drawn at one milking, so that
secretion must be proceeding at the same time. Moreover, the later
drawn portions of milk contain more solids in proportion than those
first drawn.^ Lehmann^ injected sulphindigotate of soda solution
into a vein of a milch goat, and at once had the animal milked.
No blue appeared in the milk until the udders were almost com-
pletely drawn, when there was a slight tinge. On milking the animal
again, after the lapse of an hour or an hour and a half, the milk wdiich
had collected in the udder was completely blue.

Influence of the nervous system on the secretion of milk.—
Although it is a matter of common experience that the quantity and
quality of the milk is in women materially influenced by the condition
of the nervous system, the results of experiments upon animals have
furnished evidence on this subject which is either entirely negative, or
at most of a somewhat conflicting nature. Eckhard,^ who was the first
to attempt to obtain such evidence, found no marked difference in the
milk either in quantity or quality from the udder of a goat, the nerves
(branches of external spermatic) passing to which had been cut, as
compared with the milk drawn from the other side, the nerves of which
were intact. His observations have been repeated by others,^ with
contradictory results, some having obtained an increase of secretion on
cutting the nerves, others a diminution. But even if an increase is
obtained, it has not been determined whether this is due to the
alteration in the vascular supply to the gland rather than to a direct
effect upon the gland-cells, such as is obtained in the case of the

■^ For references, see Heidenhain, Hermann's " Handbuch, " Bd. iv.

^ Die loMclwirthsch. Versucht, 1887, Bd. xxiii. S. 473.

^ Beitr. z. Anat. u. Physiol. {Eckhard), C4iessen, 1855.

* Rohrig, quoted by Heidenhain (Hermann's "Handbuch," Bd. iv.) ; de Sin^ty, Gaz.
med. de Paris, 1879, p. 593 ; Valentowicz, CentralU. f. Physiol., Leipzig u. Wien, 1888,
Bd. ii. S. 71 ; Mironow, Arch, de sc. hiol., St. P(5tersboiirg, 1895, tome iii. p. 453.


(paralytic) secretion of saliva after section of the chorda tympani.
Likewise, the effects which have been got by stimulating the cnt nerves,
and which have been usually in the direction of diminishing the
quantity of the secretion, may well be ascribed to vasomotor changes
rather than to direct nervous influence. All that can be said,
therefore, on this question is to repeat the statement, that the
experimental evidence of such an influence is still lacking, however
probable its existence may be from the everyday experience of changes
produced in the milk of nursing women, as the result of emotional

Action of 'pilocar'piiu and atro2nne.— The drug which has the most
marked effect in increasing most of the secretions of the body, namely,
pilocarpine, is stated to have little or no effect upon the secretion of
milk.^ On the other hand, atropine is well known to be constantly
employed for nursing women, in whom, for one reason or another, it
is desired to dry up the secretion. Short, however, of stopping the
secretion altogether, atropine, given in smaller doses, is found, whilst
diminishing the amount of fluid secreted, to cause the secretion of a
more concentrated milk.^

Infiucnce of diet. — The quantity and quality of the food is well
recognised as having an important influence on the quantity and quality
of the milk. The most abundant and richest milk is yielded when the
diet is liberal, and, in the case of carnivora (bitch) certainly, but less
certainly in the case of herbivora (cow), when it includes a larger pro-
portion than usual of proteid material. And it is not so much the
albuminous constituents of the milk (casein and lact-albumin) which are
increased, but especially the proportion of fat.^ This indeed has been
held to be one of the most cogent arguments in favour of the view
contended for by Yoit, that animal fat is formed mainly from proteids.*
An increase of fat in the food, without a simultaneous increase of
proteid, does not cause an increased secretion of fat in the milk.^
ISTot only the amount of proteids and fat, but also the amount of sugar,
is increased as the result of giving proteid-rich food.*' Alcohol, given to

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 93 of 147)