ON THE MECHANISM OF THE PHYSIOLOGICAL
ACTION OF THE CATHARTICS
BY
JOHN BRUCE MacCALLUM
Late Assistant Professor of Physiology in the University of California
BERKELEY
THE UNIVERSITY PRESS
1906
JOHN BRUCE MACCALLUM.
The following pamphlet was completed only a few days prior to the death
of the author, which occurred on the sixth of April, nineteen hundred
and six. Through his death Physiology was robbed of one of its most
brilliant young investigators.
John Bruce MacCallum was born in Dunnville, Canada, on the eighth day
of June, eighteen hundred and seventy-six. Through the influence of his
father, Dr. G. H. MacCallum, now Superintendent of the State Asylum
at London, Ontario, his interest in the natural sciences was early
aroused and during his college career at the University of Toronto
as much of his time as possible was devoted to these subjects, but
chiefly to biology. After his graduation in 1896 he entered the Medical
School of Johns Hopkins University. Under the influence of Professor
Mall he undertook during his first medical year an investigation
on the histogenesis of the cells of the heart-muscle, and it was
characteristic of him that he began his work in pathological anatomy
also with an original investigation. During the third year of his
medical course he again prepared several anatomical papers and at the
same time assumed the burden of the proof reading and of preparing
the index of Barker’s book on Neurology. It was during this year,
1898-1899, that the first symptoms of the disease appeared which was
to cut short the life of this talented, indefatigable worker. From
this time on he was constantly handicapped in his work by the struggle
against illness.
After his graduation in medicine in nineteen hundred he returned to
Baltimore as assistant of Professor Mall. In nineteen hundred and
one he went to Leipzig to work in the laboratory of His, but his old
enemy again interrupted his work, this time attacking him in the form
of an affection of the apex of the lungs. He returned home as soon as
sufficiently recovered to bear the journey, and upon the advice of Dr.
Osler he spent the winter in Jamaica. During this period he translated
and edited Szymonowicz’s histology into English.
The condition of his health made it impossible for him to live in the
East and in the autumn of nineteen hundred and two he went to Denver,
“where he rented an office and tried to practice. He abhorred the
life, though, and held in contempt the charlatans with whom he came
in contact. There were patients and he made enough money to pay his
expenses in the few weeks he was there, but the repugnance to that
kind of life was too great, and he abandoned his practice. They had
made him teacher of anatomy in their medical school, in charge of the
department, I believe. The students were difficult to manage--their
ideals being far different from his.[1]” The bright spot in his life in
Denver was his association with Dr. Sewall, the former physiologist.
Having accepted a call to the University of California, I offered Dr.
MacCallum a position as assistant in physiology, and we began our
work here together. During the first and second years his health was
tolerably good, but in nineteen hundred and five he undertook a problem
on immunity which was beyond his physical strength and he began to fail
rapidly. He went East to be treated by Professor Osler, returning to
Berkeley in the fall of the same year, in a much weakened condition,
but if he realized how critical was his condition he betrayed it to
no one. He was cheerful and apparently hopeful. As he was not able
to exert himself in experimental work, I suggested that he put the
results of his experiments done at Berkeley into book form.
The present volume is the result of this work, the last done before
death claimed him. It has been published without alteration. The
preface was probably written two days before his death, which came
suddenly--as he had always wished that it might.
MacCallum belonged to that type of scientists whom we may designate
as discoverers. His results were obtained quickly, were made secure
beyond doubt, and were put into such shape that they could easily be
demonstrated by him. But as is also common in the case of discoverers,
his publications were comparatively brief. This may make it at times
difficult for inexperienced or uncritical workers to repeat his
experiments. I may state, however, that they belong to the regular
class exercises of the medical students in our laboratory. Those who
have once learned how to perform them can always count upon their
succeeding.
In his work as well as in his life he was a calm thinker, the reverse
of a hustler. He conceived his experiments in the spirit of an artist
and the realization of his ideas was the poetry his work put into
his life. He did not work for outside success, nor did he pose as a
benefactor of mankind.
Those who have known him well feel that the death of John Bruce
MacCallum has left a gap which will never again be filled.
JACQUES LOEB.
BERKELEY, November 7, 1906.
FOOTNOTES:
[1] Quoted from a letter from his brother, Professor W. G. MacCallum,
of Johns Hopkins University, to whom I am under obligation for the data
given in this sketch.
PUBLICATIONS BY JOHN BRUCE MACCALLUM.
1. Fresh-water Cladocera.
University of Toronto Quarterly, May, 1895.
2. On the Histology and Histogenesis of the Heart Muscle Cell.
Anatomischer Anzeiger, Bd. XIII, 1897.
3. On the Pathology of Fragmentatio Myocardii and Myocarditis Fibrosa.
Johns Hopkins Hospital Bulletin, No. 89, 1898.
4. On the Histogenesis of the Striated Muscle Fibre and the Growth of
the Human Sartorius Muscle.
Johns Hopkins Hospital Bulletin, Nos. 90-91, 1898.
5. A Contribution to the Knowledge of the Pathology of Fragmentation
and Segmentation and Fibrosis of the Myocardium.
Journal of Experimental Medicine, Vol. IV, 1899.
6. Development of the Pig’s Intestine.
Johns Hopkins Hospital Bulletin, Vol. XII, 1901.
7. Notes on the Wolffian Body of Higher Mammals.
American Journal of Anatomy, Vol. I, 1902.
8. On the Muscular Architecture and Growth of the Ventricle of the
Heart.
Johns Hopkins Hospital Reports, Vol. IX, 1900. (Memorial volume to Dr.
W. H. Welch by his pupils.)
9. Text-book of Histology and Microscopic Anatomy. By L. Szymonowicz.
Translated and edited by J. B. MacCallum. Lea Bros., 1902.
10. On the Mechanism of the Action of Saline Purgatives, and the
Counteraction of their Effect by Calcium. (A preliminary communication.)
University of California Publications, Physiology, Vol. I, 1903.
11. On the Action of Saline Purgatives in Rabbits and the Counteraction
of their Effect by Calcium. (Second communication.)
American Journal of Physiology, Vol. X, 1903.
Also: University of California Publications, Vol. I, 1904.
12. On the Local Application of Solutions of Saline Purgatives to the
Peritoneal Surfaces of the Intestine.
American Journal of Physiology, Vol. X, 1904.
Also: University of California Publications, Vol.I, 1904.
13. On the Influence of Calcium and Barium on the Flow of Urine. (A
preliminary communication.)
_Ibid._, 1904.
14. The Influence of Saline Purgatives on Loops of Intestine Removed
from the Body.
_Ibid._
15. The Secretion of Sugar into the Intestine Caused by Intravenous
Saline Infusions.
_Ibid._
16. The Action of Cascara Sagrada. (A preliminary communication.)
_Ibid._
17. The Influence of Calcium and Barium on the Secretory Activity of
the Kidney. (Second communication.)
University of California Publications, Physiology, Vol. II, 1904. Also
in the Journal of Experimental Zoology, Vol. I, 1904.
18. Ueber die Wirkung der Abführmittel und die Hemmung ihrer Wirkung
durch Calciumsalze.
Pflüger’s Archiv, Bd. 104, 1904.
19. The Action on the Intestine of Solutions Containing two Salts.
University of California Publications, Vol. II, 1905.
20. The Action of Purgatives in a Crustacean (_Sida Crystallina_).
_Ibid._, 1905.
21. On the Diuretic Action of Certain Haemolytics, and the Action of
Calcium in Suppressing Haemoglobinuria. (A preliminary communication.)
_Ibid._, 1905.
22. The Diuretic Action of Certain Haemolytics and the Influence
of Calcium and Magnesium in Suppressing the Haemolysis. (Second
communication.)
_Ibid._, 1905.
23. The Action of Pilocarpine and Atropin on the Flow of Urine, by John
Bruce MacCallum.
_Ibid._
24. Factors Influencing Secretion.
The Journal of Biological Chemistry, Vol. I, 1906.
AUTHOR’S PREFACE.
The following pages contain an account of a long series of experiments
made to determine the action of saline purgatives. Many of the results
have been separately published in various scientific journals, and they
are now gathered together with certain new material in an attempt to
give as connected and complete an account as possible of the action of
this class of drugs.
The experiments were begun at the suggestion of Professor Loeb, to
whom I am greatly indebted for the constant interest which he has
taken in the work, and whom it is a pleasure to thank for many helpful
suggestions.
CONTENTS.
PAGE
Chapter I.--Normal Movements and Secretion of the Intestine 1
Chapter II.--The Subcutaneous and Intravenous Injection of
Saline Purgatives 9
Chapter III.--The Local Application of Saline Solutions to the
Peritoneal Surfaces of the Intestine 23
Chapter IV.--The Production of Increased Secretion of Fluid
into the Intestine by the Saline Purgatives 29
Chapter V.--The Inhibiting Action of Calcium and Magnesium
on the Movements and Secretion of the Intestine 38
Chapter VI.--The Action of Saline Solutions on Loops of Intestine
Removed from the Body 50
Chapter VII.--The Action on the Intestine of Solutions Containing
Two Salts 57
Chapter VIII.--The Effect on the Intestine of Intravenous Saline
Infusions 65
Chapter IX.--Mode of Action of the Saline Cathartics 74
Chapter X.--Possible Therapeutic Value of These Experiments 83
Chapter XI.--The Action of Purgatives of Vegetable Origin 86
CHAPTER I.
Normal Movements and Secretion of the Intestine.
A. _Normal Movements of the Intestine._
The normal movements of the intestine have been described by many
observers, and in these descriptions there is a fair amount of
uniformity. Ludwig and his pupils, Bayliss and Starling, Magnus and
others have studied this subject with much care. In such a complicated
organ as the intestine there are many sources of error, and differences
of opinion may readily arise if an attempt is made to analyze too
closely the functions of the various tissues making up the intestine,
to decide for example whether the movements are of nervous origin or
muscular, or whether the secretion is dependent primarily on the blood
supply or on the nervous system. For our purpose it will be sufficient
to regard the intestine as an organ composed of certain muscular
layers, certain nervous plexuses and certain glands--and to discuss the
action of various influences not on these separate tissues, but on the
organ as a whole, holding in mind also the nervous and bloodvascular
connections of the organ.
If the abdominal cavity of a dog, cat, or rabbit be opened under the
surface of m/6 NaCl solution or Ringer’s solution at body temperature,
it will be found that the intestines are not entirely at rest.
According to local conditions, more or less active movements will be
seen. These were described by Ludwig and others as consisting of two
kinds of motion, namely, the _pendulum movements_, and _peristaltic
movements_.
The pendulum movements are rhythmical, and consist of a regular slight
swinging of the loops upon one another. Their frequency has been
measured by Bayliss and Starling.[2] According to these observers, each
contraction and relaxation lasts 5 to 6 seconds, so that the rhythm
consists of 10 to 12 beats per minute. The rhythm is however not always
regular, the contents of the loop and other local conditions exerting
an influence. The cause of these pendulum movements is not perfectly
clear. By many they have been ascribed to a rhythmical shortening of
the intestine, _i.e._, a rhythmical contraction and relaxation of the
longitudinal muscle coat. Mall[3] regards them as arising mainly in the
circular layer; while Bayliss and Starling state that they are due to
simultaneous contractions of the circular and longitudinal coats.
The peristaltic movements consist of more or less strong contractions
of the circular coat of the intestine, varying from a slight ring-like
contraction which passes rapidly down the gut to a violent constriction
of the intestine which obliterates the lumen of the gut and passes
very slowly from above downward. The slight contractions may travel,
according to Bayliss and Starling, as rapidly as 2-5 cm. per second,
while the more violent ones move not more than ¹⁄₁₀ cm. per second.
According to Nothnagel, Mall, and others, the formation of these
peristaltic waves is always due to a local stimulus, usually the
presence of a bolus of food. The intestine contracts immediately above
the point of stimulation and the mass of food is forced downward. The
wave of contraction follows close behind the bolus, while for some
distance above this point similar waves run downward until they reach
the mass of food. The gut is usually relaxed below the bolus, and
the general statement has been made that a stimulation at any point
causes a contraction above that point and an inhibition below it.
It is generally thought that Auerbach’s plexus is concerned in the
propagation of the peristaltic wave since the peristalsis takes place
also when the intestine is separated from the central nervous system,
and does not occur when nicotine or cocaine is given to paralyze the
intrinsic nerves of the intestine.
In addition to the pendulum and the peristaltic movements, there is a
third quite distinct motion to be observed in the intestine. The normal
peristaltic movements are very slow, while this third type, called by
Nothnagel “Rollbewegung,” consists of a rapid contraction which may
pass from one end of the intestine to the other in 1 to 2 minutes. The
function of this movement is thought to be the rapid elimination of
irritating substances from the intestine. It occurs irregularly and is
more common in slight pathological conditions of the gut.
It is generally believed that the normal peristaltic wave passes only
from above downward, and never in the reverse direction. This has been
shown in many ways. Mall[4] removed a certain length of the small
intestine and reversed it so that the end which had originally been
nearer the stomach was now in the position formerly occupied by the
end nearer the rectum. The food would not pass down this part of the
intestine, but accumulated above it. In other words, the peristalsis
continued as it was before the loop was removed, the wave passing in
the reversed loop from below upward. A further illustration of the same
thing is seen in the fact that in an isolated loop an object inserted
in the gastric end of the loop will rapidly be passed to the other
end, while it is impossible to force the object into the rectal end
because of the peristaltic waves which constantly expel it. Grützner[5]
observed that the intestinal contents sometimes move backward and
forward in the intestine, and that an easily recognizable substance,
_e.g._, food introduced into the rectum _in enemata_, was sometimes to
be found afterwards in the stomach. It seems further from Cannon’s[6]
study of the cat’s intestine by means of the Röntgen rays that
antiperistalsis certainly takes place in the colon of this animal. In
the transverse and ascending colon antiperistaltic waves occur at the
rate of 5-6 per minute. No antiperistalsis was observed in the small
intestine.
_Factors which normally cause or influence the intestinal movements._
Although there has been some divergence of opinion on the subject, it
is now generally held that anaemia of the intestine causes a cessation
of all movements. This has been shown by van Braam-Houckgeest,[7]
Mall,[8] and others. Clamping of the aorta, opening of the heart, etc.,
cause all movements to cease. Hyperaemia of the intestine on the other
hand causes active movements to arise. Any conditions which cause a
venous engorgement of the intestine bring about intestinal movements.
Bokai[9] found that CO_{2}, is a direct stimulant to the intestine, and
that the movements may be stopped by the application of oxygen. Krause
and Heidenhain first noticed that when an animal’s breathing is stopped
the peristaltic movements of the intestine greatly increase, but cease
when the breathing is recommenced.
The influence of the intestinal contents upon the movements of the
gut was discussed as long ago as 1750 by Foelix.[10] Among the later
authors to treat of this subject is Bokai. In addition to indigestible
and irritating substances taken in with the food, there are certain
substances ordinarily formed in the intestine by decomposition which
cause peristaltic movements. Among these are CO_{2}, CH_{4}, and
H_{2}S. All of these gases which are more or less constantly formed
help in keeping up the normal movements of the intestine. Certain
faecal constituents have also the same effect. Bokai mentions among
these a number of organic acids--lactic, succinic, butyric, formic,
propionic, acetic, caproic, and caprylic acids. There is no doubt also
that the salts taken in with the food exert a considerable influence.
The intestine is to some extent also under the influence of extrinsic
nerves. As shown by Pflüger,[11] the splanchnic nerves exert an
inhibitory action on the intestine, so that their section causes
intestinal movements and their stimulation brings about a cessation
of peristalsis. This has been ascribed by some authors to the
vasomotor action of the nerves. Concerning the action of the vagus
there has been difference of results. Many experimenters have found
that stimulation of this nerve causes contractions of the intestine.
Others have obtained no results. If, however, the splanchnics be cut
and the inhibitory impulses abolished, stimulation of the vagus gives
constant results consisting of a slight inhibitory action followed by
an increase of the rhythmical contractions of the intestine.
B. _Normal Secretion Into the Intestine._
It is probable that under normal conditions a fluid is secreted from
the entire length of the intestine, but this fluid undoubtedly differs
somewhat in the various parts. The duodenum with Brunner’s glands, the
jejunum and ileum with the glands of Lieberkühn and the large intestine
in which there is a preponderance of mucus cells may be assumed to
give secretions which are not identical. The methods which have been
used to obtain the succus entericus for analysis are subject to
criticism, and much remains to be discovered with regard both to the
mechanism of secretion and the nature of the normally secreted fluid.
The most fruitful method has been that instituted by Thiry,[12] and
later modified by Vella.[13] This consists of the establishment of a
permanent fistula from the intestine through the skin from which the
intestinal juice may be gathered after complete healing has taken
place. This is commonly known as a Thiry-Vella fistula. In general
it has been observed that practically no fluid is secreted into the
intestine without a stimulus of some sort. Electrical or mechanical
stimulation as well as the introduction of food causes a yellowish
fluid to pour into the gut. Pregl[14] has studied the secretion by
this method in a lamb. Here he finds a continuous secretion which
is increased after the taking in of food. It possesses a distinctly
alkaline reaction, and contains carbonates, chlorides, and a
considerable quantity of proteid. It also contains urea. For a complete
analysis the reader is referred to Pregl’s article. The intestinal
juice of the lamb has no digestive action on proteids. There was formed
from starch paste a fermentable sugar. Cane sugar and maltose were
inverted, but milk sugar remained unchanged.
The influence of the nervous system on the secretion of intestinal
fluid is very clear. It was found by Moreau[15] that section of the
nerves to the intestine brought about a large secretion of fluid
into the intestine resembling closely that obtained by a Thiry-Vella
fistula. Budge[16] had previously noted that extirpation of the ganglia
of the coeliac plexus caused an increase of fluid in the intestine.
The results of Moreau, who carried out his experiments with isolated
loops, have been repeatedly confirmed, and some question has arisen
as to the nature of the fluid secreted, some authors regarding it as
a transudation, others as a true secretion. It has been compared by
some to the rice water stools of Asiatic cholera, and on account of the
analogy with the secretion which pours from the salivary gland after
section of the chorda tympani it has been called a paralytic secretion.
Landois[17] ascribes the secretion to the cutting of vasomotor nerves
which causes circulatory changes so marked that a transudation of
fluid occurs. In the leg, however, it has been shown that the normal
transudation and lymph formation are not increased by section of the
nerves. One would also expect to find oedema of the intestinal wall
if this were a process of transudation due to vascular changes. Such
oedema does not occur.
The nature of the fluid obtained by section of the nerves to the
intestine has been studied by many investigators. Moreau described it
as a light yellow clear fluid with a strongly alkaline reaction. Its
specific gravity is 1.008. It contains carbonates, chlorides, organic
materials and a little urea. According to Hanau,[18] the fluid contains
no digestive ferments, although in the dog he found that in the first
part of the secretion fibrin was digested to some extent and starch
converted into sugar. This he ascribed to the presence of pancreatic
juice. Mendel[19] has recently worked on this subject and finds also
that the pure paralytic secretion has no digestive action on fibrin,
but that there is a slight amylolytic action. Cane sugar and maltose
are inverted, while milk sugar is not.
The fact that the paralytic secretion resembles very closely the normal
secretion both physically and chemically seems to indicate that it is a
true secretion and not a transudation.
Bottazzi[20] has recently found that an extract of the small intestine
injected into the blood causes not only an increase in the fluid
secreted into the intestine, but also an increase in the peristaltic
movements. This extract is an aqueous one, the nucleoproteids being
precipitated by acetic acid. It thus contains the secretin of Bayliss
and Starling and is capable of increasing also the pancreatic
secretion. The fluid produced in the intestine was later analyzed
by Bottazzi and Gabrieli[21] and proved to be quite similar to the
normal intestinal secretion. It is of some interest to note that the
intestinal secretion and the pancreatic secretion are simultaneously
augmented by the intravenous injection of this extract.
FOOTNOTES:
[2] Journal of Physiology, Vol. XXIV, 1899, p. 99.
[3] Johns Hopkins Hospital Reports, Vol. I, 1896.
[4] _Loc. cit._
[5] Deutsch. Med. Wochenschr., XV, 1899.
[6] Amer. Journ. Physiol., Vol. VI, 1902.
[7] Pflüger’s Archiv, VI, 1872; VIII, 1874.
[8] Johns Hopkins Hospital Reports, I, 1896.
[9] Arch. f. exp. Path. u. Pharm., Bd. 23-24.
[10] De Motu peristaltic. intest. Treviris, 1750.
[11] Über das Hemmungsnervensystem f. d. peristal. Bewegungen d.
Darmes, Berlin, 1857.
[12] Sitzungsb. d. k. Akad. d. Wissensch. Wien, 1864, Bd. 1.
[13] Untersuchung. z. Naturl. d. Mensch. u. d. Thiere; 1881; Bd. XIII.
[14] Arch. f. d. gesammte Physiologie, Bd. LXI, 1895, S. 359.
[15] Centralbl. d. Medicin. Wissensch., S. 209, 1868.
[16] Verhandl. d. K. K. Leop. Carol. Akad. d. N., Bd. 19, 1860.
[17] Lehrbuch der Physiologie, 10th Ed., p. 360.
[18] Zeitsch. f. Biologie, Bd. 22, 1886, p. 195.
[19] Arch. f. d. ges. Physiol., Bd. 63, 1896, p. 425.
[20] Arch. di Fisiologia, 1904, I, 413.
[21] Arch. internationales de Physiologie, 1905, Vol. III, II, p. 156.