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

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Bradford obtained no secretion on stimulating these nerve-filaments.

Secketion due to a Keflex Action of Peripheral G-anglia.

We may reject the view of Bernard,^ that a secretion can be
obtained from the submaxillary gland of the dog, by means of nervous
impulses passing from the mucous membrane of the tongue by the
lingual nerve to the " submaxillary " ganglion, and thence to the gland.
The direct proof alleged in favour of this view was that occasionally,
after section of the chordo-lingual, direct stimulation of the tongue, or
the application of ether, caused a slight secretion. As no anaesthetics
were given, it is quite possible that a slight flow from the duct might be
caused by reflex movements. The result was not obtained by Eckhard,
Bidder, and others ; and until it can be obtained with some constancy,
and after administering at any rate a moderate amount of anaesthetics, it
may properly be disregarded.

The indirect proof alleged is that after section of the chordo-lingual,
stimulation of the lingual on its course to the tongue (the nerve being
cut and the central end stimulated) causes a secretion from the sub-
maxillary gland. This, in fact, is commonly the case. The amount of
the secretion, broadly speaking, increases the nearer the electrodes are to
the chorda tympani. It is often barely more than perceptible. The
fact observed by Bernard, that three to five days after section of the
chordo-lingual, a secretion could no longer be obtained, seems sufficient,
with our present knowledge of the central nervous system, to show that
the lingual secretion cannot be reflex in the ordinary sense.

There can be little doubt that Schiff's ^ explanation is in the main
correct, namely, that some secretory fibres for the submaxillary gland,
instead of running to it direct by the chorda tympani, accompany the
lingual for a short distance and then run back to the gland. Schiff

^ Journ. de Vanat. et physiol., etc., Paris, 1864, tome i. p. 507. For some further
account of the earlier papers, see Foster's "Text-book of Physiology," 1879, Srd edition, p.

^ "Lecons sur la physiol. de la digestion," 1867, tome i. p. 284.


seems to have thought that these recurrent fibres ran in a single bundle
a considerable distance down the lingual, for he says that when the
lingual nerve is cut about 2 cm. beyond the point where the chorda
tympani leaves it, and time is allowed for degeneration, no secretion is
obtained by stimulating the central end ; a negative result which was
not obtained by Wertheimer.^ Wertheimer's positive result then may
be taken as showing that the recurrent fibres leave the lingual at more
than one spot.

But it is nevertheless possible that on stimulating the central end of
the lingual a secretion should be obtained which is not produced by
recurrent fibres, and which is due to nervous impulses passing through
local nerve-cells. The nerve-cells on the course of the chorda tympani
are, as we have seen, scattered ; if the chorda tympani fibres branch
before running to these cells, stimulation of one of the branches would
probably cause a nervous impulse to pass to the more central branches
and to the cells connected with them. This would be a reflex through
efferent fibres of the kind described in some other peripheral ganglia.^
Such action with the actual anatomical arrangements is more likely to be
obtained from the sublingual than from the submaxillary gland. It
would, of course, be annulled by degeneration of the chorda tympani.

Direct Ieritability of Gland-Cells.

It is natural to suppose that stimulation of the gland-cells by
electrical, chemical, or mechanical stimuli should be capable of causing a
secretion. There is, however, no direct evidence that this is the case.
After atropine has been given, no secretion has been obtained ; but it
must be mentioned that, even when the nerve-endings in the sub-
maxillary gland are in a full state of irritability, it is difficult to obtain
secretion from it by electrical or other stimuli applied to its outer sur-
face, and which do not affect the internal bundles of nerves.^

Extirpation of Salivary Glands, Injection of Saliva into

THE Blood.

The extirpation of all the salivary glands is, of course, impossible ;
but the large salivary glands, i.e. those which secrete by far the greater
portion of the saliva, can be cut out. This has been done by Fehr.*
He states that in the dog he removed not only the parotid, submaxillary,
and sublingual glands on both sides, but also the orljital glands. The
operation had no appreciable effect on nutrition ; and the only difference
in the liehaviour of the animal was that it drank more water. A
similar result was observed by Schafer and Moore.^ They removed
from a dog the parotid, the submaxillary, and the larger part of the sub-
lingual glands. There was no disturbance of nitrogenous metabolism,
and neither sugar nor alljumin appeared in the urine. Carbohydrates

^ Arch, dc'physiol. norm, ctimtli., Paris, 1890, p. 519.

^ Langley and Anderson, Journ. Flmjsiol., Cambridge and London, 1894, vol. xvi.
p. 410.

^Bernard ("Leijons sur la propriiites physiologiques," etc., 1859, tome ii.) found, by
stimulating the gland directly, that pain was caused.

* Henle and Meissner's Jahresb., in Ztf<chr. f. rat. Med., 1862, p. 255.

'' " Proc. Physiol. Soc. ," 1896 p. xiii., Journ. Physiol., Cambridge and London,
vol. xix.


were well digested, and the animal throve on a diet of liread and

The salivary glands, then, in the domestic dog, appear to Ije rather
a convenience than a necessity, and there is no evidence that they have
any " internal secretion " ; carl^onic acid passes from the gland-cells to
the blood, but. there is no indication that any other substance does so.

Saliva injected into the blood is much less harmful than might be
expected. Bernard,^ indeed, injected considerable quantities into a vein
of a dog to which no anaesthetics had been given, and did not observe a
result of any kind. Extracts of the salivary glands injected into the
blood cause a temporary fall of blood pressure,^ Ijut so many suljstances
in solution do this that the action cannot be regarded as specific.

General Considerations ; Theories as to the Mode of Action
OF Secretory Nerves.^

The facts which show that secretory nerve-fibres exist in the cranial
nerves are so well known, that it is not necessary to consider them in
detail. It is sufficient here to recall the fundamental facts, that secre-
tion may in each salivary gland take place at a pressure higher than
that of the blood supplied to the gland, and that nerve-fibres end in
connection with the gland-cells.*

In the case of the sympathetic, the comparatively slight amount
and the transitory nature of the secretion, render the question less clear.
It was in fact suggested,^ early in the history of sympathetic saliva,
that the cervical sympathetic nerve causes a secretion solely in con-
sequence of the pressure exercised on the gland-cells by the contraction
of the blood vessels, brought about by stimulation of the nerve. Such a
view offers a plausible explanation of many of the facts relating to the
secretory action of the sympathetic, such as the normal small quantity
of the secretion in the dog, the increased quantity after the cranial nerve
has been stimulated, the rapidity with which the maximum rate of the
" augmented " saliva is attained, the normal absence of reflex secretion
by way of the sympathetic when sapid substances are placed on the
tongue, and the absence of effect of atropine and pilocarpine upon the
secretory function of the sympathetic.

But a closer inquiry shows, nevertheless, that this view is untenable.
On the general theory it may be noted, that the constriction of the small
arteries of the gland in all probability decreases the pressure on the
gland-cells instead of increasing it. On the experimental side, we may
mention three points.

1. The constriction of the blood vessels has at times no relation to

^ " Lecons de pliysiol. exp(?,r.," 1856, p. 141.

^ Schafer and Oliver, Joiwn. Physiol., Cambridge and London, 1895. voL xviii. p. 277.

^ For a general historical account of the views which have been held with regard to
secretion, I may refer the reader to Prof. Gamgee's Address to the Biological Section of the
British Association in 1882, and to Prof. Heidenhain's Introductory Account in Hermann's
"Handbuch," 1880, Bd. v. Th. 1, S. 1-13.

■* Cf. Fusari et Panasci, Arch. ital. de hioL, Turin, 1891, tome xiv. ; G. Eetzius,
Biol. Untersuch. , Stockholm, 1892, IST. F., Bde. iii., iv. ; Korolkow, Anat. Anz.,
Jena, 1892, Bd. vii. S. 580; A. Dogiel, Arch. f. mikr., Anat. Bonn, 1893, Bd. xlii. ;
Berkeley, Johns Hoplcins Hosp. Sep., Baltimore, 1894, vol. v. ; C. Arnstein, Anat. Anz.,
Jena, 1895, Bd. x. S. 410; G. C. Huber, Journ. Exper. Med., Baltimore, 1896, vol. i.
p. 281.

sGrtinhagen, Ztschr. f. rat. Med., 1868, Bd. xxxiii. S. 258.


the flow of saliva. Thus, on stimulatmg the cervical sympathetic in the
dog, it may happen that the secretion does not begin until the pallor of the
gland and the reduction of blood flow are about maximal ; the slow flow
of sahva may then continue without change in the blood flow, and may
even continue after the end of the stimulation, when the blood vessels
are dilated. In the cat, contraction of blood vessels without any flow
of saliva can be easily observed by stimulating the sympathetic after
about 30 mgrms. of atropine have been injected into the blood.

2. The quantity of saliva obtained by squeezing the gland is less
than that obtained by stimulating the sympathetic. This is most
readily observed in the submaxillary gland of the cat, in which about
ten times as much saliva is usually obtained by stimulating the sympa-
thetic as by squeezing the gland.

3. The total amount of saliva obtained by stimulating the sympathetic
is, in some cases, too great for it to be obtained by simple expression of
fluid from the gland. This is perhaps most striking in the case of the
augmented secretion of the submaxillary gland of the dog. In favour-
able circumstances, i to ^^ c.c. of saliva may be obtained by a single
continuous stimulation, and with a diminution in the size of the gland
not appreciably greater than would be accounted for by the dimmution
in the amount of blood in it.

Some of these observations, it will be observed, negative also the
possibility that the sympathetic saliva can be due to pressure exercised
by contractile tissue other than blood vessels around the alveoli.

We conclude, then, that both the cranial and the sympathetic nerves
contain fibres which end in connection with the gland-cells, and which
are capable of causing changes in the cells leading to secretion; and
we pass on to consider whether the secretory nerve-fibres are of more
than one kind. There are two possibilities to take into account : — first,
whether there are fibres inhibiting the secretion as well as fibres excit-
ing the secretion ; and, secondly, whether there are fibres causing
chemical changes in the gland distinct from those which cause the flow
of fluid.

The former possibility we may treat briefly. Until it is shown that
the decrease in the blood flow through the gland which the sympathetic
causes is insufficient to account for the decrease in the flow of saliva
which the sympathetic at times produces, this hypothesis of inhibitory
fibres does not need serious attention.

The second possibility we must consider more at length. The
theory of the existence of two kinds of nerve-filjres in secretory nerves
is due to Heidenhain.'^

According to this theory, the secretory fibres proper cause certain
unknown changes in the cells leading to the passage of fluid through
them. The trophic flbres cause chemical changes in the cells leading,
on the one hand, to the growth of protoplasm, and, on the other, to the
conversion of the stored-up secretory matei-ial into a more soluble form.
Further, according to this theory, the proportion of these two kinds of
nerve-fibres is different in cranial and sympathetic nerves. The cranial
nerve contains more secretory than trophic fibres. The sympathetic
nerve contains more trophic than secretory fibres.

The trophic filjres, it will l^e observed, have two functions, not
necessarily connected with one another. The evidence that they cause

' Heidenhain, Hermann's "Handbuch," 1880, Bd. v. (1) p. 78.


a growth of protoplasm is derived from the microscopical examination
of the various glands, after stimulating the sympathetic. Thus,
according to Heidenhain — to take the most striking example adduced
by him — if the cervical sympathetic be stimulated in the dog for several
hours, there is no secretion from the parotid gland, l;)ut the gland-cells
show a great increase in carmine-staining material, i.e. a considerable
growth of protoplasm.

I have not been able to convince myself that any considerable
changes of this nature take place. On stimulating the sympathetic the
thick secretion usually stops up the ducts, and if any further secretion
takes place it can only pass out into the lymph spaces. After •
stimulating the sympathetic for five to seven hours, I do not find any
marked increase in the staining power of the cells ; and the fresh gland
either shows no outer non-granular zone at all, or a very small one.

The evidence that a separate class of trophic nerve-fibres exists,
which converts stored-up material into a more soluble form, rests on
certain facts, which we will discuss as far as possil)le separately. In the
first place, there are the facts adduced to prove that soluble substance is
formed during secretion, and which do not touch the question whether
the formation is due to a special nerve-fibre or not.

1. It was shown by Heidenhain that the percentage of organic
substance in saliva, secreted under the influence of the cranial nerve,
increases with the rate of secretion. On this fact Heidenhain argued
somewhat as follows : If the solvent power of the fluid passing through
the cells remains constant, and the solubility of the stored-up substance
in the cell also remains constant, the amount of the stored-up substance
dissolved by the fluid in its passage through the cell will decrease as the
rate of its passage increases. For, below saturation point, the amount
dissolved must decrease the less the time the solvent is in contact with
the solvend. But, in fact, the slower the passage of the solvent the less
it dissolves ; hence, with increasing rate of flow, there must be either an
increase in the solvent power of the fluid, or an increase in the solubility
of the stored-up substance. Heidenhain considered that in mucous
saliva, at any rate, the only substance which could increase the solvent
power of the fluid was sodium carbonate. And this salt, he found, did
not increase, as saliva was secreted more rapidly. In consequence,
he concluded that the substance in the cell must become more soluble.
An increase in solubility of part of the stored-up substance was then a
result of stimulating nerve-fibres.

But it is by no means clear that the rapidly-secreted fluid is not a
better solvent than the fluid secreted slowly. Werther, working in
Heidenhain's laboratory, found in fact that the percentage of sodium
carbonate in the submaxillary saliva of the dog does increase, though
but slightly, with the rate of secretion of saliva. And, in addition, it
cannot be regarded as certain that sodium chloride and other neutral
salts do not aid in the solution of the substances stored up in the cells.
The evidence, indeed, seems to me to be on the other side. And, as we
have seen, when saliva is secreted more rapidly, there is an increase in
the percentage of salts as well as in that of organic substances. Finally,
the statement that the faster the fluid passes through the cell, the less
substance it will dissolve, depends on the assumption that in slowly-
secreted and in rapidly-secreted saliva, the fluid has an equal oppor-
tunity of dissolving the stored-up material. This is not necessarily the


case ; the more rapidly-flowing fluid might pass more freely into the
intracellular spaces, and come into more intimate contact with the
mucous or other stored-up material of the cell.

2. Better evidence of the formation of soluble substances in gland-
cells, under the action of nerve stimulation, is afforded by the after-action
of strong nerve stimulation. If, between two weak stimulations of a
cranial nerve, a strong stimulation of the same nerve or a stimulation
of the sympathetic nerve be introduced, the second weak nerve
stimulation gives rise to saliva containing a higher percentage of organic
substance than that produced by the first similar stimulation. The
fact may be taken as showing that the strong stimulation, introduced
between the two weak ones, has converted slightly soluble into more
solulile material, which has only partially been carried out of the cell.
But this is not the only possible explanation. We can imagine that the
stronger the stimulus the more the fluid passing through the cell will
be brought into contact with the stored-up substance, with the result
that more of this substance will absorb water and pass a stage on the
way to solution than would otherwise be the case. And consequently,
for some time after a strong stimulus, any fluid passing through the
cell would find substance already on the way to solution or already
dissolved, without any alteration in its chemical composition.

The experimental evidence, then, of the formation of a soluble
substance during secretion is not satisfactory. And, in fact, it is
doubtful whether the glands contain any stored-up organic substance
in a " comparatively insoluble " state. The granules of the glands are
seen to enter readily into solution — micellar or other — when a crushed
piece of the gland is irrigated with dilute alkaline salt solution. The
mucin or mucins of saliva have not been shown to be different from the
mucin or mucins contained in the salivary glands. The mucous material
of the glands is often spoken of as mucigen, following the analogy of
trypsinogen and pepsinogen ; but it is well to remember that there is
nothing to show that trypsinogen and pepsinogen are less soluble in
dilute saline solution than trypsin and pepsin ; and further, that there is
some evidence that the oesophageal glands of the frog secrete pepsinogen
as such, and not as pepsin.

Supposing, however, it were shown that nerve stimulation causes an
increase in solubility of secretory material, it would still remain to show
that this change is caused by a special class of nerve-fibres ; and to this
part of the theory we may now pass.

It was thought that direct proof of the separate existence of trophic
fibres was afforded by the results on the parotid gland of stimulating
the sympathetic in the dog. Stimulation of the sympathetic caused no
flow of saliva, but caused nevertheless histological changes in the
gland-cells, and a great increase in the percentage composition of the
saliva obtained in otlier ways. Here was apparently an instance of
nerve-fibres producing the changes demanded of the trophic fibres, by
hypothesis, and producing no others.

But we have seen (p. 498) that the sympathetic is capable, in
favourable circumstances, of causing a flow of saliva from the parotid
gland of the dog. Since, then, secretory fibres are present in the
sympathetic strand supplying the parotid, the action of the nerve in
this particular instance cannot, without further examination, be taken to
show the existence of an additional class of nerve-fibres.


We come, then, to a comparison of the relative effects of the cranial and
sympathetic nerves as the final part of the evidence for the existence of
two classes of nerve-fibres. It is said that the difference in the percentage
composition of sympathetic saliva, and of that produced by stimulating
the cranial nerve, can only be satisfactorily explained by supposing that
secretory and trophic fibres are present in both, and that the number
of trophic fibres relatively to the secretory is greater in the sympathetic
than in the cranial nerves.

This conclusion seems to me to lie legitimate and unavoidable, if a
diminution in the blood supply to the glands brought about by vaso-
constrictor nerves does not markedly increase the percentage of organic
substance in the saliva secreted. But this, so far, has not been shown
to be the case (cf. p. 508). The question can hardly be settled until
means are found of stimulating the sympathetic vaso-constrictor fibres
of the salivary glands without stimulating the sympathetic secretory

We find, then, that the hypothesis of a separate class of trophic
fibres, although affording a convenient explanation of a certain number
of facts, can hardly be considered proved at any point. It presents also
certain difficulties of its own which we need not insist on here.

On the whole, I think the most probable view is, that only one
kind of nerve-fibre runs to the gland-cells, and that this causes all the
changes in the gland-cells which are capable of being caused by nerve
stimulation. These changes include the taking up proteid material
from the lymph, some katabolic action — shown by the setting free of
carbonic acid — and changes leading to the passage of water and salts
through the cell. It is not improbable that the nervous impulses hasten
the conversion of absorbed proteid to secretory substances, and it is
perhaps possible that they increase the solubility of the secretory sub-
stance already formed. The effect of the secretory fibres, as regards
the amount and percentage composition of the saliva obtained, would
naturally vary with the strength of the stimulus, the condition of the
gland at the time, the quality and quantity of the blood flowing through
the gland.

The exact processes which take place in gland-cells and which lead
to secretion is at present outside the range of our knowledge. The high
secretory pressure naturally suggests osmosis as the cause of the passage
of water and of salts. And, about five and twenty years ago, the view
that secretion is due to the formation in the cells of a substance of high
endosmotic pressure was put forward by Hering and others. Much
more is known now of the phenomena of osmosis than was known then ;
but the nature of the process is still so obscure, that to attempt to
explain secretion on the lines of osmosis is to venture on httle better
than conjecture.

It may, however, be worth Avhile to state briefly some points regarding the
relation, or possible relation, of osmosis to secretion.

We will consider, first, what facts of secretion we could in some sort
account for, on the theory that osmotic pressure is of the same nature as
gaseous pressure, and assTiming that osmosis does take place in the gland- cells.

The facts which it seems most feasible to offer an explanation of are, the
occurrence of secretion when the cells are stimulated and not at other times,
the increase in the rate of flow during stimulation, the increase in the per-
centage of salts in saliva with increase in the rate of flow.
VOL. I.— 34


"We may speak of tlie alveolar cells as forming a membrane, and call the
part towards the l3-mph the outer laj-er of it, and the part towards the lumina
of the gland the inner layer. In the inner layer are spaces containing soluble
organic substance.

The explanation of the above-mentioned facts on the osmotic theory might
be as follows : — The membrane is impermeable in the unstimulated state ; on
stimulation, a rearrangement of its molecules takes place, so that, of immedi-
ately adjoining portions, parts are permeable to water and parts are permeable
to salts also, whilst parts remain impermeable. On increasing the strength of
the stimulation, a larger and larger area of the membrane becomes permeable,
and of this a proportionately larger and larger part becomes permeable to

The increase in the percentage of organic substance in saliva, which accom-
panies increased rate of flow, might be due simply to the greater percentage
of salts causing an increase in the solvent power of the fluid, or to a larger
proportion of the fluid passing into the spaces of the inner layer.

Proteid molecules do not pass through the gland-cells, but they enter it,
and are deposited, forming the outer non-granular zone ; the process is spoken

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 75 of 147)