utilization by the system of the ordinary products of proteolysis.
The latter, as we have seen, are mainly proteoses and peptones, and
yet all the evidence points clearly to the fact that these substances
are never present, at least in any quantity, in the blood or lymph,
even when digestive proteolysis is at its height. Further, the very
nature of the proteoses and peptones, their marked physiological action
when they are introduced directly into the circulating blood, their
rapid excretion, either as proteoses or peptones, by the kidneys when
so introduced,[207] all indicate that they are foreign substances,
totally out of their natural environment when introduced into the
blood-current. And yet we very well know that proteoses especially are
possessed of high nutritive qualities; they are abundantly able to
support animal life. Thus, Politzer[208] found by feeding experiments
with heteroalbumose, dysalbumose, and protoalbumose, that these bodies
taken into the stomach have the same nutritive value as meat. Various
feeding experiments with proteoses from different sources, carried out
in my laboratory on young dogs, have shown conclusively that for short
periods of time, at least, these hydrolytic cleavage products are fully
as capable of sustaining the nitrogenous equilibrium of the body as the
proteids from which they are derived. In fact, the results obtained
favor the view that the proteoses, weight for weight, possess a higher
nutritive value than fresh beef.[209] It may be questionable, however,
whether such a result would follow in experiments conducted over longer
periods of time, but of this we may be certain, that the proteoses
formed in the alimentary tract can be absorbed and utilized by the
system without their exerting any toxic action whatever.
[207] Franz Hofmeister: Ueber das Schicksal des Peptons im Blute,
Zeitschr. f. physiol. Chem., Band 5, p. 125.
[208] Ueber den Nährwerth einiger Verdauungsproducte des Eiweisses,
Pflüger’s Archiv f. Physiol., Band 37, p. 301.
[209] Compare Hildebrandt, Zur Frage nach dem Nährwerth der Albumosen,
Zeitschr. f. physiol. Chem., Band 18, p. 120.
Consequently, we are forced to the conclusion that these primary
products of proteolysis, so important in the nutrition of the animal
body, must undergo some change during the process of absorption, by
which they are converted into new bodies, less toxic in their nature,
and better adapted for the direct nutritional needs of the organism.
The same statement applies likewise to peptones.
The fact that peptones are not discoverable in the blood and lymph,
even during or after active digestion, was practically ascertained
years ago by such well-known workers as Maly, Adamkiewicz, and others.
The natural supposition following this observation was that the
products of proteolysis underwent some change in the hepatic cells; but
this view was soon shown to be untenable by examination of the portal
blood, which was found to be as free from peptone as the blood of the
hepatic vein. Neumeister,[210] using the more modern methods of work
and with the wider knowledge gained during these latter years, has
shown conclusively that proteoses and peptones are never present in
the blood, even when these substances are contained in the intestine
in fairly large amounts. I can corroborate these statements from the
results of my own experiments in this direction. Thus, I have taken a
dog in full digestion, fed with an abundance of meat, and collecting
the blood from the carotid artery have made a careful examination
for peptone, by the following method: The blood was allowed to flow
directly into a dilute solution of ammonium sulphate, sufficiently
strong to prevent coagulation, and then shaken with ether to rupture
the red blood-corpuscles. The solution, freed from ether, was next
saturated with crystals of ammonium sulphate, by which the proteid
matter was completely precipitated. The clear filtrate was then
concentrated somewhat, the excess of the ammonium salt removed by
filtration, and the filtrate carefully tested for peptone by addition
of a large volume of a saturated solution of potassium hydroxide and
a few drops of a dilute solution of cupric sulphate. The test was
wholly negative, although the intestine of the animal showed the
presence of both peptone and proteoses. This result, as I have said,
is simply confirmatory of work done by others in this direction,
notably Neumeister, and illustrates the statement that peptones are
not to be found in the circulating blood, even after a full proteid
diet. In this connection it is to be remembered that we have abundant
proof of the rapid disappearance of both proteoses and peptones[211]
from the intestine, either by absorption or otherwise. They certainly
disappear, and, as we have seen, are not to be found in the blood.
Further, Neumeister has confirmed the original observation of
Schmidt-Mulheim,[212] that both chyle and lymph are practically free
from proteoses and peptone, thus again forcing us to the conclusion
that the primary products of proteolysis must undergo change prior to
their passage into the blood or lymph.
[210] Ueber die Einführhrung der Albumosen und Peptone in den
Organismus, Zeitschr. f. Biol., Band 24, p. 277.
[211] Rohmann: Ueber Secretion und Resorption im Dünndarm, Pflüger’s
Archiv f. Physiol., Band 41, p. 440.
[212] Du Bois-Reymond’s Archiv f. Physiol., p. 33, 1880.
Many observations lend favor to the view that a transformation of
some kind takes place in the intestine itself, not indeed in the
lumen of the tube, but somewhere in the walls, through which the
peptones must pass before reaching the blood. Thus, peptones placed in
contact with pieces of the isolated, though still living, intestine,
after a time completely disappear from view,[213] so completely that
no reaction can be obtained even by the most delicate of tests. In
support of this statement I may cite the results of several of my
own experiments which certainly furnish evidence that true peptones
undergo profound alteration by simple contact with the living mucous
membrane of the small intestine. The method employed was similar to
that made use of some years ago in a study of the influence of peptone
on the post-mortem formation of sugar in the liver.[214] A large,
well-nourished rabbit was killed by severing the carotid artery and the
blood collected and defibrinated. Of this, 50 c. c. were mixed with an
equal volume of 0.5 per cent. salt solution containing 1.25 grammes of
pure amphopeptone, prepared from egg-albumin, the mixture obviously
containing 1.25 per cent. of peptone. The fluid was transferred to a
large, roomy flask, provided with a stopper having two holes, in one
of which was fitted a long glass tube reaching below the fluid. The
flask, with its contents, was then placed in a suitable water-bath at a
temperature of 40° C.
[213] Salvioli: Eine neue Methode für die Untersuchung der Functionen
des Dünndarms, Du Bois-Reymond’s Archiv f. Physiol., 1880. Supplement
Band, p. 112. Neumeister: Zur Physiologie der Eiweissresorption und zur
Lehre von den Peptonen, Zeitschr. f. Biol., Band 27, p. 324.
[214] Chittenden and Lambert: Studies in Physiol. Chem., Yale Univer.,
vol. i., p. 171.
The small intestine of the rabbit was carefully separated from the
mesentery and from the pancreatic gland, and the upper portion cut
open and quickly washed free from any contained matter or adherent
secretions, by repeated immersion in 0.5 per cent. salt solution warmed
at 40° C. This was repeated until the tissue was quite free from all
impurities, after which it was cut into small pieces and immersed for
a moment in a 0.5 per cent. solution of sodium chloride containing
1.25 per cent. of peptone. The tissue was then carefully collected on
coarse muslin, allowed to drain, and then quickly transferred to the
flask containing the warm blood and peptone. This mixture was kept at
40° C. for two hours, a slow current of air being bubbled through the
fluid during the entire period. At the expiration of this time the
fluid was separated from the pieces of tissue by nitration through
muslin, and then saturated with ammonium sulphate after the usual
method for the separation of albumoses, etc. On now testing a portion
of the clear filtrate for peptone by the biuret test, not a trace of
a reaction could be obtained. The entire amount of proteid matter
present was precipitated by the ammonium salt, thus showing that the
peptone originally added had been completely transformed into something
precipitable by saturation of the fluid with ammonium sulphate. That
this transformation of the peptone was accomplished mainly through the
action of the intestine, was shown by a parallel experiment, in which
all of the above conditions were duplicated, omitting only the pieces
of intestine. Here, however, on testing the filtrate from the ammonium
sulphate-precipitate, a strong biuret reaction was obtained, thus
proving the presence of at least some unaltered peptone.
This experiment is almost a counterpart of one reported by Neumeister,
and like his, testifies to the probability that the peptones formed in
the alimentary tract, as a result of proteolysis, undergo retrogression
through the agency of the epithelial cells of the intestinal walls
during their absorption. I have tried similar experiments with
deuteroproteose, notably with deuterocaseose, and have obtained
corresponding results. The same method may be employed as that already
outlined, although of course the deuterocaseose is in great part
precipitated by saturation with ammonium sulphate. Still, this form
of deuteroproteose, β deuterocaseose, as I have elsewhere noted, is
very slowly precipitated by the ammonium salt. Consequently, it is an
easy matter to demonstrate that this proteose, on treatment with the
intestinal mucosa in the presence of blood at the body-temperature,
is transformed into something completely and readily precipitable by
ammonium sulphate; the filtrate from the latter failing to show any
biuret reaction, although the corresponding control experiment without
the intestine gives a bright violet color with cupric sulphate and
potassium hydroxide.
Hence, we are certainly justified in saying that both peptones and
proteoses undergo some retrogression when in contact with the walls of
the intestine. Moreover, there is some evidence that the proteoses,
before undergoing such a transformation, are first converted into
peptone by the action of the intestinal walls, a statement which will
apparently apply to both the primary and secondary proteoses. This
primary action of the intestinal walls is not considered as due to any
adherent trypsin, or to possible traces of succus entericus, but rather
as a part of the action of the living epithelial cells, or perhaps as
connected with the possible presence of lower organisms not removable
from the intestinal wall by ordinary washing.
The transformation of peptones by the substance of the intestine
is apparently common to the intestinal tract of many animals, and
perhaps to all, and indeed can also be accomplished by the liver.[215]
This latter fact is of some importance, since it adds weight to the
supposition that this peculiar action of the intestine cannot be due
to the possible presence of trypsin; a view which is strengthened by
the fact that a glycerin-extract of the intestine has no action on
amphopeptone. Certainly, the latter shows no diminution in the strength
of the biuret reaction after long contact at body temperature with
such an extract. Further, it has been shown that antipeptone, which
is not affected by the pancreatic enzyme, suffers the same change
as amphopeptone by contact with the intestine. Far more probable is
it that retrogression or transformation of peptone by the substance
of the intestine, is due to the vital activity of some or all of
the epithelial cells of the intestinal mucosa; a characteristic
possibly shared by some or all of the hepatic cells of the liver. The
kidney-cells certainly do not possess this power, but we can see a
special fitness in the liver-cells being endowed with the ability to
quickly break down, or transform, any peptone or proteose that might by
chance escape unaltered from the intestinal tract. Shore,[216] however,
inclines to the view that the hepatic cells do not possess this power
to any great extent, in opposition to the older views of Plòsz and
Gyergai,[217] as well as of Seegen[218] and of Neumeister.
[215] Neumeister: Zeitschr. f. Biol., Band 27, p. 332.
[216] On the Fate of Peptone in the Lymphatic System, Journal of
Physiol., vol. xi., p. 528.
[217] Ueber Peptone und Ernährung mit denselben, Pflüger’s Archiv f.
Physiol., Band 10, p. 536.
[218] Zur Umwandlung des Peptons durch die Leber, _Ibid._, Band 37,
p. 325.
With reference to the action of the stomach-mucosa on proteoses, it
has been shown[219] that when relatively large amounts (5 grammes)
are introduced into the stomach of a rabbit, the pylorus being
ligatured, both proteoses and peptones may appear in the urine, thus
indicating that while they may be absorbed to some extent under the
above conditions, the proteoses are not readily transformed into
native proteids without exposure to the intestine. Smaller amounts
(2 grammes), however, may, under the above conditions, be completely
transformed; at least Hildebrandt claims this to be the case, mainly on
the ground that after the introduction of albumoses into the stomach,
the pylorus being ligatured, no trace of them can be found in the
urine. The same observer also claims that blood-serum, in the case of
dogs, is able to transform albumoses into ordinary serum-globulin.
Certainly, after intra-venous injection, proteoses disappear from the
blood, but, as we shall see later on, a certain amount, at least, may
be transferred to the lymph. It is also claimed that when albumoses
are injected subcutaneously, neither albumoses nor peptones are to be
detected in the urine. This, however, seems hardly probable in the
light of what has been said, and especially in view of the fact that
Neumeister’s experiments tend to show that even 0.1 gramme of albumoses
introduced subcutaneously may give rise to temporary albuminuria.
[219] Hildebrandt: Zur Frage nach dem Nährwerth der Albumosen,
Zeitschr. f. physiol. Chem., Band 18, p. 180.
Assuming for the moment that the chief products of proteolysis,
_i. e._, the proteoses and peptones, are, during the act of absorption,
transformed through the vital processes of the epithelial cells of the
intestine into serum-albumin, or globulin, and absorbed as such into
the blood, we may well consider whether such transformation, _i. e._, a
retrogression into a native proteid again, is inconsistent, or out of
harmony, with the general character of the changes known to occur in
the body. In attempting to answer this question we need not look far
to find a perfectly analogous case. Thus, in the digestion of starchy
foods by the amylolytic ferments of both the saliva and the pancreatic
juice, the carbohydrate material undergoes hydration with formation
of dextrins and maltose, the latter, at least, being quickly absorbed
into the circulating blood. But large quantities of sugar in the blood
are certainly inimical to the well-being of the organism, and we find
in the liver a tendency for the sugar to undergo a transformation,
_i. e._, a retrogression into glycogen, either through simple
dehydration or otherwise. Further, with reference to the possible
conversion of proteoses into peptone by the substance of the intestine,
we have a perfectly analogous case in the behavior of the intestinal
mucous membrane toward maltose, the final product of amylolytic action.
Thus, according to the recent work of M. C. Tebb,[220] the mucous
membrane of the intestine has the power of transforming maltose into
dextrose; simple warming at 40° C. of a solution of maltose in 0.5 per
cent. sodium carbonate with a few grammes of the dried mucous membrane
from the intestine, being sufficient to insure a marked conversion of
maltose into the higher-reducing sugar, dextrose. This observation,
I can confirm from experiments just completed in my own laboratory.
This action is presumably due to a ferment, which, according to Tebb,
is widely distributed throughout the body, being present not only
in the intestine, but also in the liver, kidney, spleen, striated
muscle-tissue, and, indeed, in the blood-serum; so that it would appear
that nearly all the tissues of the body are endowed with the power of
transforming maltose into dextrose. These statements being correct, it
would seem that, while the amylolytic ferments of the several digestive
juices transform, by hydrolytic action, starchy foods into maltose,
the latter is exposed during its passage through the intestinal wall,
as well as in the blood itself, to another ferment which carries the
hydration still further, with formation of dextrose; and yet the latter
product is destined, in part at least, to undergo retrogression into a
starch-like body, _i. e._, glycogen, before it is completely utilized
by the system. Thus, the analogy between these carbohydrate bodies and
the products of proteolysis is complete, and we may well accept the
statements already made regarding the ultimate fate of the proteoses
and peptones formed during proteolysis, as in no way inconsistent with
the general tenor of events going on in the body.
[220] On the Transformation of Maltose to Dextrose, Journal of
Physiol., vol. xv, p. 421.
While we are inclined to believe that the chemical changes attending
the absorption of proteoses and peptones occur mainly in the epithelial
cells of the intestinal mucosa, and that there is a direct transference
of the alteration-products to the blood, there are still other views
that cannot be wholly ignored. Thus, the view originally advanced by
Hofmeister,[221] in which special stress is laid upon the functional
activity of the leucocytes of the adenoid tissue surrounding the
intestine, demands some consideration. The theory supposes that these
cells not only have the power of taking up peptones, but also of
assimilating and transforming them into the cell-protoplasm. This view
being correct, it is plain that the so-absorbed proteid must pass into
the circulating blood through the thoracic duct, and Hofmeister further
considers it probable that the lymph-cells of the mesenteric glands can
transform any absorbed peptone that may escape the leucocytes of the
adenoid tissue.
[221] Zeitschr. f. physiol. Chem., Band 4.
In apparent harmony with this view is the fact that the leucocytes in
the adenoid tissue of the intestine are greatly increased in number
during digestion.[222] Furthermore, it is a well authenticated fact
that the proteoses or peptones found in pus are contained in the
pus-cells themselves, and not in the fluid in which the corpuscles
float.[223] In support of the first statement, Pohl,[224] in his recent
study of the absorption and assimilation of food-stuffs, has emphasized
the marked increase in the number of white blood-corpuscles in the
circulating blood after the ingestion of proteid foods, especially
such as meat, Witte’s peptone, and gelatin-peptone. It is to be noted
further that the increase is most marked at about the third hour after
the taking of food, viz., at a time when digestive proteolysis would
naturally be at its height. Moreover, the maximal increase, according
to Pohl’s data, is astounding, amounting as it does in many cases to
a hundred per cent. Thus, in one instance, in the case of a dog, the
number of white blood-corpuscles per cubic millimetre of blood was
8,689; yet two hours after the feeding of 100 grammes of meat the
number increased to 17,296 per cubic millimetre, followed six hours
after by a return to the original figure.
[222] Arch. f. Exp. Pathol. u. Pharm., Band 20 and Band 22.
[223] Zeitschr. f. physiol. Chem., Band 4, p. 268.
[224] Arch. f. Exp. Pathol. u. Pharm., Band 25, p. 31.
This indicates the general tenor of Pohl’s results, which have been
taken, by some physiologists at least, as confirmatory of Hofmeister’s
views; the interpretation naturally being that digestive proteolysis
in the alimentary tract is accompanied by a rapid production of new
leucocytes in the lymph-spaces surrounding the intestine, and followed
by a rapid transference of the corpuscles from their point of origin
to the circulating blood, from which they gradually disappear as
their material is made use of in the different parts of the body. In
harmony with this view, Pohl finds that there is a much larger number
of leucocytes in the blood and lymph flowing from the intestine of
an animal in full digestion, than in the arterial blood coming to
the intestinal tract. Further, when due consideration is given to
all the circumstances attending the circulation of the blood through
the abdominal organs, in connection with the great increase in the
number of leucocytes during digestive proteolysis, it seems not
unreasonable to suppose that some proteid matter might be transferred
from the intestine to the blood during the digestive period of six
or eight hours. Moreover, if Pohl’s views are correct, we see that
a portion, at least, of the proteid food-product may be transformed
into organized material in the body of the lymph-cell prior to its
passage into the blood, thus harmonizing with the statement already
made regarding the utter lack of proteoses and peptones in the blood
and lymph. This obviously means an upbuilding of the ordinary products
of digestive proteolysis into the living protoplasm of the leucocytes
in the intestinal walls, implying, however, that the transformation
is accomplished solely by the leucocytes themselves, and not by the
epithelial cells of the intestine.
I have given this brief summary of Pohl’s work because it is so closely
in harmony with the original views of Hofmeister, and because it
offers an easy explanation of one possible way in which some of the
products of digestion might perhaps pass from the intestine into the
blood. I am inclined to believe, however, that the so-called digestive
leucocytosis, which unquestionably does exist, is not a direct result
of digestive proteolysis in general, but rather an indirect result,
coming from the stimulating action of the nuclein, contained especially
in animal cells. Thus, it is a significant fact, as Pohl himself
reports, that wheat-bread, with its fairly large amount of proteid
matter, and which is fully capable of nourishing the animal body, fails
to exert any influence on the number of leucocytes in the blood. Yet we
know that the gluten and other proteids of wheat-flour are converted
by digestive proteolysis into proteoses and peptones, with the same
general properties as like products of animal origin.
In this connection we may note the experiments of Horbaczewski,[225]
which show that nuclein administered to a healthy man will give rise
to a very marked increase in the number of leucocytes in the blood.
Thus, a few grammes of nuclein may produce as striking a condition
of leucocytosis as a large amount of proteid food, due no doubt to
proliferation of the lymphoid elements of all the lymphatic tissues
of the body. Horbaczewski has reported that the mere injection of
0.25 gramme of nuclein, in the case of rabbits, will cause marked
enlargement of the spleen, with striking karyokinetic changes.
Hence, it may be assumed that whenever nuclein is set free in the
body, leucocytosis may result, provided the nuclein passes into the
circulation and is not decomposed immediately after its liberation.
[225] Monatshefte f. Chemie, Band 12, p. 246.