NERVES.

If one were to ask the physiologist: What do you expect us to find in

our anatomical investigations on the nerve-endings in the submaxillary

gland, he would undoubtedly answer: “You will find an arrangement

analogous, if not similar, to that in the striped muscle; the

nerve-fibre will be seen to approach the alveolus, penetrate its

covering, and the protoplasm of the nerve and the gland-cell will be

found to come in contact, if not to coalesce.” And that is what has been

found by Pflüger.

It has been my endeavor for some time to find something similar to the

descriptions of Pflüger, but so far in vain, although many an alveolus

has been carefully examined, flattened out and slowly crushed, so that

each nucleus could be diagnosed, but never have I found anything which

would remind me of the drawings by Pflüger in Stricker’s ‘Histological

Handbook.’

In this matter I reasoned thus: If there are any such structures as

specialized nerve-endings present in the glandular elements, we might

look for an analogy either to the striped muscle fibres or to the

capillaries, in both of which nerve-endings are known to be present. In

the former case we have the so-called end-plate—the nerve fibre ends in

a multi-nucleated mass—but as the muscle fibre, standing for a number of

cells, is so different a structure from the gland-cells, we might, with

greater probability, expect some such arrangement as we see on the

capillaries. Here we see fine fibrils, provided with nuclei, exceeding

the fibres two to four times in thickness, entwining the capillary, thus

coming in contact with each of the cells composing the capillary wall.

In the (submaxillary) gland there are similar structures to be

influenced; at least in the capillary as well as in the gland, we have

cells lying side by side to be influenced by nerves—hence we might

expect similar structures.

Although the books in general have very little to say about the nerve

supply of the capillaries, yet it is a fact, and can well be

demonstrated, _e. g._, in the frog’s muscle, that such is the

arrangement. As a rule, the fibril cannot so readily be detected, but

the nuclei belonging to it are not difficult to recognize. A still more

convenient and instructive locality is the base of the frog’s mouth,

where everything is one plane, and where the nerve fibres can be

followed to their ultimate ramifications.

Let us now see what evidence of nerve-endings we find in or on the

alveoli of the gland, examining one, or more accurately, a part of one

(the round eminence). We shall see what fig. 1 presents. We see there

two sets of nuclei; one kind oval, longish, stained lighter than the

rest, of a pink hue (fig. 1, _m_), and these a further examination will

demonstrate to be the nuclei belonging to the membrana propria, which

have also been described before. Besides these nuclei, fewer in number,

there is another kind, making up the bulk of the nuclei, more rounded in

form (fig. 1, _g_), and of a deep-red color, which, in their turn, will

prove to be the nuclei of the gland-cells; and these two are the only

elements or structures that I have been able to demonstrate in a

glandular alveolus.

At one time I thought I had found in or on the alveoli the evidence of a

network of fine nerves. Quite frequently one can observe longish, even

spindle-shaped, often deeply stained, nuclei, which resemble very much

those belonging to the fine nerve fibres. (Fig. 2, _n_, such nuclei are

figured.) But so far, whenever I examined such a spindle-shaped nucleus

more carefully, I found that it proved to be one of the nuclei belonging

to the membrana propria, already described, and the form, as well as its

dark color, was due to the fact that it had been examined edgewise. If,

by manipulation, such a nucleus was turned over and compressed to

present a flat surface, it would have an oval outline and be of a

light-red color. Fig. 3 (_a_, _b_, _c_), shows the same nucleus as it

appeared when seen edgewise, when seen from the flat and when seen in a

position midway between these. Thus is also to be explained the

demilune: If the section would strike a nucleus so that it would be seen

only edgewise—especially if the membrana propria has a chance to roll up

slightly—we should then have a deeply stained body, somewhat

half-moon-shaped, the demilunes of the books.

So far, nothing but the nuclei have been mentioned, and the observation

might very appropriately be made, that there might exist some

exceedingly fine and delicate nerve fibrils without nuclei. Such a

system of structures would, of course, be almost impossible to

demonstrate with any degree of certainty. I have not, of course,

sufficient reason to deny such an arrangement, and would not consider it

improbable if we had not, in the capillaries of the frog’s muscle (and

other structures) evidence certainly not in favor of such an assumption.

The fine nerve fibrils supplying the capillaries are richly supplied

with nuclei, although the cells which build up the walls of the

capillary are by far more insignificant elements than the secreting

cells of the gland. Certain it is that as yet there is no evidence of

the existence of such fine non-nucleated fibrils, arranged either in the

form of a network or a bundle of fine branches.

The examination of the alveoli not leading to any results as to

nerve-endings—no structures being discovered there that might be called

nervous—I attacked the problem from the other side. I took up the nerve

trunks accompanying the ducts, and tried how far I could follow their

divisions and branches, and can say that I have spent a great deal of

time on this point. In speakings of the bloodvessels, the fact was

mentioned that, where arteries and veins of any size run along-side of

the duct, these are accompanied by nerve branches, _i. e._, bundles of

nerve fibres, inclosed in a sheath, and these—at least in the cat, the

calf and the ox—are made up (excepting, possibly, the very large trunks)

of fine nerve fibres. Thicker or medullary nerves I have not been able

to discover, even in branches of considerable size, consisting of, say

six or eight fibres, and giving off smaller twigs containing one to

three fibres. Fig. 7 shows such a nerve-trunk with side branches;

neither in the main stem nor in the offshoots are there any medullary

nerves discoverable.

If this observation is correct, we see that what has to be traced

further, is not the more easily recognized medullary fibre, but

exceedingly fine fibrils carrying in certain intervals nuclei, the only

distinguishing feature. It will be admitted also (first) that it must be

a matter of considerable difficulty to follow such indifferent looking

structures, as delicate fibres. And (secondly), one cannot expect to

find medullary nerves approach the alveoli, penetrate the membrane, come

in connection with the secretory cells, etc., etc, as has been done by

Pflüger. If the question should be asked how far I have been able to

follow these nerves, I should say: Small twigs consisting of one to

three fine fibrils, enclosed in a sheath branch off from a trunk, not

much larger, and apply themselves to the membrana propria of the duct;

their sheaths in all probability coalescing with that membrane. Here

they have been seen to apply themselves to some bloodvessel and are now

lost out of sight, being hid by all the many structures mentioned above,

the nuclei of membrane, capillary, duct cells, and the fibre cannot so

readily be distinguished from the membrana propria of the duct upon

which it rests. But I do not wish to be understood that because the

nerves have been lost out of sight, along-side of vessels, that they

have their “ending” there, inasmuch as the network of bloodvessels is

such a close one that the nerves cannot but help coming in contact with

them. Fig. 8 shows such a fine nerve-trunk. By the aid of aniline blue

the fine fibrils have been made quite plain. Such fine fibrils can by

the same means be demonstrated in much larger trunks, as shown in fig.

7, and it can be shown that even such large trunks consist of nothing

but these fine fibrils.

I have also seen, exceptionally however, fine nerve twigs run into the

alveoli directly, but the nerves here were of the same nature as the

ones described going to the duct. Fig. 9 shows a fine fibril passing on

to an alveolus and running probably on to a vessel; the nerve fibre

resting upon gland cells, also stained, could not with absolute

certainty be traced to the vessel. There is a small break shown in the

drawing.

As intimated, especially if the cells of the duct are still _in situ_,

it is impossible to follow the fine nerve-fibres any further. By

pressing out the cells from the ducts, one can obtain portion of the

duct, with the capillaries belonging to them, but they are short pieces,

and the nerve fibril is not easily discoverable.

But there remains one fact to be mentioned, which may throw light on the

question, as to how the nerves end and which in my opinion might and

does clear up the difficulty.

Examining the capillaries supplying the gland alveoli, one is able to

find nuclei, not belonging to the capillaries themselves. This statement

can be made for two reasons. In the first place, the majority of these

nuclei have not the form of the nuclei of the capillary, and in the

second place these nuclei are situated on the outside of the capillary

wall. Whoever has examined the capillaries of the frog’s muscle knows

that just such or the same nuclei belong to nerve-fibres, supplying the

capillary wall. In the mammal of course these nuclei are smaller and not

so conspicuous, nor can we procure pieces of capilliary of any length

(the structures under examination here, not being in one plane.) Thus we

cannot expect to have matters so plain here and easy of demonstration.

After finding these nuclei, it was of course my desire to find if they

were united by fibres. It must in this matter be kept in mind, that if

there are such fibres present to which these nuclei belong, these may be

expected to be in the most intimate relation with the capilliary wall,

if one is to influence the other—and therefore not of ready and easy

demonstration.

I have, however, succeeded in showing in a number of instances that such

fibres exist. Figs. 10 and 11 show such a fibre uniting several nuclei.

The shortness of these fragments makes a more perfect demonstration

almost impossible.

If this observation is correct, we find on the capillaries the same

(only finer) fibres provided with nuclei, which we have lost out of

sight following the branching out of the nerves.

There is also some evidence of fine fibres in the membrana propria of

the ducts, inasmuch as we find here nuclei along-side of the

capillaries, these not being the nuclei of the membrane, but resembling

altogether the nuclei of the nerve fibres.

Again, as stated above, I have not been able to find any such evidence

of nerves in connection with the gland cells themselves. In case,

however, such an arrangement or something similar existed, why should it

have been impossible for me to find evidences of such as well here on

the gland cells as on the capillaries; and should they not be more

readily found in the gland than in the capillary, inasmuch as we have

larger structures to deal with here in the gland.

The conclusion then regarding the nerve-endings to which my work has led

me are these:

There were no special nerve-endings found in connection with the gland

cells themselves. _We find, however, upon the capillaries evidence of

the same kind of fine nucleated fibrils, which we find to be present in

the fine nerve twigs_, as far as we can follow them in their course

towards their final distribution. To explain the action of nerves on the

process of secretion we would have to assume either that the nerves

accompanying the capillaries also influence the gland cells, or that the

glands are stimulated to activity by some changes in the condition of

the capillary wall furnishing a greater amount of oxygen and nutritive

fluids.

The results are partly negative, partly positive. The latter I wish to

emphasize, believing it worthy of attention, as it may throw light on

the physiology of the capillary wall, which seems to be altogether too

much neglected. The negative I have offered, knowing well enough that

such negative results must be accepted as final with much hesitation.

To any one feeling inclined to undertake investigation on this gland, I

would make a few suggestions:

(1) Make sections through gland hardened in bichromate of potash,

or alcohol, and stain with staining fluids.

(2) Compare in material prepared as above described, the vascular

supply of duct and gland substance proper.

(3) Compare gland and duct cells.

(4) Find the nuclei of the membrana propria and compare the same

with the nuclei of the gland cells.

(5) See if you can examine the same nucleus from different sides.

Do you think that the demilune of books and the nucleus of the

membrana propria might be the same thing?

(6) Prepare pieces of the membrana propria covering the alveoli.

What is your opinion—is there a membrane or only a reticulum of

connective tissue cells?

(7) Prepare pieces of membrana propria of duct.

(8) Can you find the nuclei of the duct, and other nuclei on the

exterior of the capillaries?

(9) Can you find pieces of capillaries belonging to the alveoli,

and do you find any nuclei on them?

(10) Examine the wall of the duct in injected and uninjected

material, both stained.

(11) Follow the bloodvessels—can you find nerves on the walls of

arteries?

(12) Of what structure do you find the root of a little lobule to

consist?

(13) How do the nerve trunks differ from the fibrous envelope

holding together all these structures?

(14) Differentiate between the nuclei of the nerve fibres and the

nuclei of the nerve sheath.

(15) Examine nerve branches of various thicknesses—what do you

find the nature of the nerve fibres to be? Do not forget the

aniline blue and try other staining fluids.

(16) Can you find evidence in the alveoli of other structures

besides capillary, membrana propria and salivary cells?

(17) How far have you succeeded in following the fine nerve twigs?

(18) By all means try different methods, different tissue, and

compare the results. See what you can discover by simply teasing

material treated with Muller’s fluid, and other stained and

treated as I have described.

(19) Follow the course of the arteries, and note where the larger

vessels pass into the capillaries.