Aksel Odd Dines Haneborg.

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49363 04i91i








Paa grundl^g av naervaerende avhand-
ling er forfatteren kreert til doctor

ved Det Kongelige Frederiks Uni-











Chapt. I. Analytical method 1

Recovered of the contents of the stomach and

flushing of the latter 2

Determination of the free and combined hydrochlo-
ric acid, the total acidity and the hydrogen-ion-con-
centration 4

Determination of the proteolytic capacity of the

gastric juice 9

Determination of alcohol 13

Determination of tartaric acid and tartar in claret
and rhenish wine 19

)) II. The effects of alcohol upon resorption and secretion
in the digestive canal, with special reference to the
stomach 20

» III. The influence of alcohol upon the proteolytic ef-
fects of the natural contents of the stomach ... 38

» IV. The relation of alcohol to the secretion in the stom-
ach and the composition of the contents of the stom-
ach, with direct effects in the stomach 44

1. Test meals with and without alcohol 46

2. The effects of alcohol upon diseases of the
stomach 54

a) Ulcus ventriculi 55

b) Cancer ventriculi 58

c) Dyspepsia 60

d) Achylia gastrica 65

3. Investigations concerning the effects of conside-
rable doses of alcohol upon the secretion of
gastric juice in healthy individuals 69

)) V. The effects of alcohol upon »psychic« secretion . . 73

» VI. The influence of alcohol upon the motor functions

of the stomach 82

» VII. Experiments with wine and beer 91

» VIII. Resume and discussion of the results of the experi-
ments 1^7

1. The effects of alcohol upon conditions of resorp-
tion 107

2. The influence of alcohol upon the proteolytic
effects of natural gastric contents in vitro ... 110

3. The relation of alcohol to secretion Ill

4. The effects of alcohol upon the psychic secretion

of gastric juice 113

5. The influence of alcohol upon the motor functions

of the stomach 113

6. The effects of beer and wine upon gastric dige-
stion 113

7. The effects of alcohol with a pathological condi-
tion of the stomach 114

Bibliography 118


The clinical experiments with various patients and
convalescents mentioned in this thesis were carried out at the
medical section of the Christiania Municipal Hospital, under my
former master Dr. H. J. Vetlesen, M. D., Senior Physician, whom
I hereby convey my special thanks.

The continued experiments were carried out at the medical
Policlinic of the Riks Hospital, by kind permission of Professor
S. Laache, M. D.

The other experiments and special physiological-chemical in-
vestigations were carried out at the University Physiological
Institute, the principal of which Professor S. Torup. M. D. has
with never failing interest helped me with advice. I hereby
offer him my most sincere thanks.

Christiania, May 1921.

Aksel 0. Haneborg.


The object of the investigations of which an account will
be given in the following pages is to offer a contribution to-
wards an understanding of the effects of alcohol upon a number
of processes which take place in the stomach during the pre-
sence of food in the latter.

It is quite true that there has been no lack of research in
this direction. From ancient times alcohol was renowned as a
!»stomachicum« that was able to promote and facilitate digestion.

Most of the earlier investigators, however, restricted them-
selves for the most part to an examination of the effects of al-
cohol upon the proteolysis of the pepsin. This is of course a
matter of great importance, but it is nevertheless only one in-
dividual factor. For indeed, digestion is not merely dependent
upon this purely chemical process, but also depends upon the
nature of the secretion, both of the qualitative composition and
quantity of the gastric juice which is secreted. In addition there
is the circumstance that the conditions of evacuation of the stom-
ach undoubtedly play a vital part both in the purely objective
result of the treatment of the food and also as regards the sub-
jective condition of the body during digestion. The incomplete-
ness of the earlier investigations becomes still more striking when
we notice that the great majority of these investigations were
carried out with preparations oi pepsin which are on the mar-
ket, and carried out with more or less haphazard preparations
of concentrated hydrochloric acid, even though they may have
been close to the normal, and in glass. If we are to draw con-
clusions with regard to the effects of alcohol upon digestion, the
investigations must naturally approach as closely as possible to

the actual conditions present, and must deal with all the factors
which have influence upon them. We should first and foremost
investigate the relation of alcohol to the secretion itself both in
a qualitative and quantitative respect, and next the course of
digestion in the stomach itself, and finally the conditions of
evacuation of that organ.

For an understanding of the results of digestion in the stom-
ach, it will be necessary to investigate the effects of the na-
tural contents of the stomach upon proteolysis in vitro and the
conditions of resorption of alcohol in the stomach.

The investigations have been laid so close to the physiolo-
gical and practical conditions occurring in ordinary life in order
that they may be of greater value for the understanding of the
alcohol question on the whole. In addition, experiments have
also been made with various patients in order to find the effects
of alcohol upon a diseased condition of the stomach.

The investigations therefore fall into the following sections : —

J. Analytical method.
II. The resorption of alcohol from stomach and intestines.

III. The effeco of alcohol upon digestion with the natural con-
tents of the stomach in vitro.

IV. The relation of alcohol to the secretion in the stomach
and the composition of the contents of the stomach, with
direct effect upon the latter.

V. The effects of alcohol upon psychical secretion.

VI. The effects of alcohol upon the conditions of evacuation
of the stomach.

VII. Investigations of the effects of ale and wine upon the
processes of secretion in the stomach and the evacuation
of the latter.

VIII. Discussion of results, and r^sum^.

I. Analytical Methods.

Before proceeding to deal with the special investigations
and their results, we will give a general survey of the methods
of procedure and the analytical methods employed in order to
avoid repetition and interruptions.

As test meals there were at times employed those generally
known to medical literature and at others such as were composed
with a view to the special objects of these investigations.

As regards the special meals, an account will be given of
each experiment at which they were employed. As regards the
others, Ewald's test breakfast was employed in the following
combinations :

250 ccms of warm water and one roll of wheaten bread
weight 40 grammes. Time of meal 10 min. Instead of a
roll, 40 grammes of wheaten bread were now and then

For a BOURGETFABER meal there were employed:
250 grammes of oatmeal gruel, 50 grammes of minced
and boiled veal, 80 grammes of wheaten bread, buttered,
eight boiled prunes and two tablepoons of cranberry
preserve. Time of meal fifteen minutes. In the experi-
ment with claret and Bhenish wine there were employed
for Boiirget^s meal: 150 grammes medium thick oatmeal
gruel, the water (100 ccms) being removed, and instead
there are given 100 grammes claret or 100 grammes Bhenish
ivine respectively. Otherwise the same constituent parts.
In the experiment with ale, there were given: 25 grammes
of oatmeal porridge (with corresponds to 250 grammes of
gruel) and 225 grammes of ale.

Recovery of the contents of the stomach
and flushing of the latter.

For the recovery of the entire contents of the stomach
there was employed an ordinary stomach pump, and for pumping
a Senoran flask.

For the recovery of small tests from the contents of the
stomach and intestines respectively there was employed a
Mehfuss probe, a quite thin stomach-intestine probe in which is
placed a small pierced metal olive. For pumping, a small glass
syringe was employed. This so-called Rehfuss gastro-duodenal
tube can without inconvenience to the patient lie during the
whole of the period of digestion in the stomach or intestine
respectively. Now and then small specimens of the contents
may be taken for closer examination. I have taken tests of
from 5 to 10 ccms at intervals varying from 15 minutes to one
hour. By means of the gauge marked on the rubber tube we
can determine how far we have reached in the intestine if we
succeed in getting it past the pylorus. In this way we can
also take specimens of the contents of the stomach at various
layers, up by cardia and down by fundus, in order to investigate
whether there is the same composition at various layers.

By experiments on animals, it has been proved th^t in the
lowest layer at fundus ventriculi there is found a larger quantity
of gastric juice, and for that reason digestion proceeds
more strongly there. In two or three cases I took various
tests at the uppermost part from cardia and at the lowermost
part from fundus, having beforehand by soundings and measure-
ments convinced myself what the distance was from the teeth
to cardia.

After a Bourget meal there at first appeared no free
hydrochloric acid either up by the cardia or down by fundus:
and the total acidity was the same for both tests (14 and 19
in the two tests respectively). After the lapse of one hour, two
different tests were again taken. There was then found at
fundus HCl. 13 and HCl. 39, and in the region about cardia
HCl 14 and HCl 34 respectively, in the two tests. In the
same way tests were made at various depths of the stomach in
order to investigate whether there might be any difference in

the concentration of alcohol at various layers. In one test with
ale drunk with an Ewald meal there was found after 45 minutes
a concentration of alcohol = 35 % for both tests. Sufficiently
large tests (10 ccms) were taken to secure against error from
mixing the tests in the stomach probe itself.

There can thus scarcely be any essential difference in the
percentage of alcohol at the various layers in the stomach, at
any rate at the commencement of the digestive process. On
the other hand it is possible that during the meal, when the
contents of the stomach after the lapse of some hours have
become more digested, there may be found a difference in the
<5oncentration of acid nearest to the walls of the stomach, so
that it is greater there than above and in the. midst of the
contents of the stomach. This is supported by the last of the
above-mentioned tests, in which the total acidity was 68 and 72.

The peptic strength in these tests was not investigated for
lack of gastric juice.

In all experiments there was ensured beforehand that the
stomach was empty at the beginning of the experiment. If
found necessary, washing out was performed. When in the
experiments we speak of «gastric juice » we mean thereby the
contents of the stomach.

In determining the quantity of the contents of the stomach,
the latter was first emptied by means of an ordinary stomach
pump, and was then washed out with a certain quantity of
water. I then placed this aside in a measuring glass for
twenty-four hours, and determined the volume in ccms. of the
sediment. For the determination of the remainder I employed
the Mathieu-Remond formula.

With regard to the time taken for withdrawing the food,
and the hour for taking up the gastric juice etc., care was
always taken to secure that Ewald's test hreakfast was eaten in
exactly ten minutes, and removal was performed forty-five
minutes after the meal was finished. For Bourget-Faber' s meal
15 minutes was allowed for eating, and removal was performed
three hours after.

The reason why a period of three hours was selected in
the latter case is that I desired to have as wide limits as
possible in my experiments in order that it might be easier to

prove any possible difference between the two test meals to be
compared. If we wait too long — more than three hours —
we run the risk of all the contents of the stomach having left
that organ^ so that we have no means of finding out how far
gastric digestion has proceeded, for normally a Bourget-Faber
meal should have left the stomach after the lapse of three to
five hours according to the Faber investigations. (Kemp) (88).

Determination of the free and combined hydrochloric acid,
the total acidity and the hydrogen-ion- concentration.

According to L, Michaelis (108) the free hydrochloric acid
is that which is present in the gastric juice in greater quantities
than the quantity corresponding to the equivalent of pepton.
The combined hydrochloric acid is that which is situated between
the free hydrochloric acid and the isoelectric point.

For volumetric analysis of the free hydrochloric acid, there
were formerly employed various methods such as that of Reoch,.
Koster, etc., until Mintz (115) proposed Gilnzlurg's reagent.
Morner (183) employed Kongo paper, and Topfer (162)
Dimethylamidoazohemol. Amongst other indicators proposed
are: — ultra marine, malachite green, benzopurpurine, fuchsine,.
emerald green, tropaolin etc.

After Arrhenius^ theory of dissociation, determination by
means of titration and indicator was regarded as less reliable,,
the theory having shown that the proportions of acid do not
remain constant in a liquid during titration. For by the
addition of Na OH the equilibrium of the liquid is so disturbed
that little by little the HCl will be free. Therefore titration
always gives too high figures. Both Michaelis and S. P. L.
Sorensen (156) have proved this further, and maintained that
the titration method cannot be used for the investigation of
HCl. We do not obtain the correct figures. Instead we must
use the hydrogen-ion-concentration method, either the electro-
metrical or the colorimetrical method.

Comparative experiments for the determination of hydrogen-
ion-concentration and titration have been carried out by
various investigators. Thus Tangl (158) Foa (49) and Frankel
(51) used the electrometrical method for the determination of the-

hydrogen-ion-concentration and compared it with the titration
method in gastric juice.

Johanne Christansen (30 and 31) has undertaken compara-
tive investigations in this matter. She considers that doubtless
it is not possible to find the exact concentration of hydrogen-
ion in the gastric juice by the titration method, but that
nervertheless we can find the free HCl. in the contents of the
stomach by an exellent method of titration which gives quite
good results as regards the concentration of hydrogen-ion.
For the free HCl is the most important source of hydrogen-
ion in the contents of the stomach. She urges the following:
- — «0f course the determination of the hydrogen-ion-
concentration and that of the free HCl are two quite different
things. But we can compare the two methods of investigation
in those cases where we have to deal with strongly acid
gastric juices, the dissociation of the free hydrogen-ions being
so considerable that they constitute the most essential factor of
the entire hydrogen-ion-concentration. »

By comparing the figures obtained, Johanne Christiansen
found that the gastric juice varies both when quite pure and
when it is derived from an Ewald test breakfast or from a
Bourget meal.

This is due to the albumen and peptones in the contents of
the stomach by which the HCl is kept bound. This HCl is
then dissociated by the addition of NaOH during titration.

According to Johanne Christiansen, Giinzburg^s reagent is
an admirable indicator for the determination of the free HCl
during titration. It is also serviceable for the determination of
the hydrogen-ion-concentration, as the errors thereby arising
are not so large.

When kept in the thermostat, it is found that the free and
bound HCl alter after the lapse of hours and days. The
Giinzburg figures decrease, the Kongo figures remain unchanged,
whilst the Phenolphtalein figures increase. This was shown by
Ambard and Foas (4). It is due to the circumstance that the
free HCl unites with the amino groups formed during

With regard to titration with Giinzburg^s reagent and
dimethylamidoazobenzol in order to find the free HCl, Michaelis

— 6 —

does not agree with Johanne Christiansen. The former considers
that dimethylamidoazobenzol is better than the elaborate
Giinzburg titration and points out that the error he finds in
titration with dimethylamidoazobenzol is due to the fact that the
two points of reaction — the salmon pink and the lemon-yellow
— are not noted. The salmon pink reaction point corresponds
to a hydrogen-ion-concentration: Ph ~ 2.5 and the lemon
yellow Ph — 4.0.

According to Michaelis we also find free HCl by titration
with dimethylamidoazobenzol to salmon pink, as the gastric
juice does not then contain any more free HCl. The bound
HCL lies between the salmon-pink dimethylamidoazobenzol
titration and the isoelectric point, i. e. a Ph =6 — 7.

According to Michaelis the reaction point of phenolphaltein
lies at Ph = 8.2. Litmus paper has a reaction point at Ph :=z
6.5 (according to Johanne Christiansen Ph = 7). According
to Michaelis the bound HCl. occurs as peptonhydrochloride
arising at hydrolysis.

In these experiments dimethylamidoazohenzol was employed
for the titration of gastric juice. In a manner similar to that
of Michaelis there are also recorded the two points of reaction^
the salmon pink and the lemon yellow, and in the experiments
they are recorded in such a way that the figures which corres-
pond to the salmon pink reaction are recorded as HCl, and
the figure which corresponds to the lemon yellow is given in
parenthesis, e. g. HCl. 18 (24). When only one figure is given
it applies to the salmon pink reaction (free HCL).

Simultaneously with the dimethylamidoazobenzol, of which
only one drop of a 1 % alcoholic solution is employed,
phenolphthalein is added and the point of reaction with phenol-
phtalein is read off on the first appearance of a red colour.
Titration is performed with O.l n NaOH.

For a determination of the actual hydrogen-ion-concentration
in the gastric juice I have employed the colorimetric
method according to S. P. L. S0rensen (156). There is
employed, as suggested by Sorensen, the hydrogen-ion exponent
Ph as expression for the of hydrogen-ion-concentration («the
reciprocal* value of the Brigg logarithm applied to hydrogen-
ions*), for we jhave the condition that hydrogen-ion-

concentration with increasing Ph decreases and does not

S. P. L. Sorensen has further worked out the colorimetric
method. For this there are used various mixtures of salt, weak
acids and bases, which Henderson terms «pushers». Of these
pusher mixtures Pels (48) employed mixtures of vinegar and
sodium acetate or ammonia and ammonium chloride respectively.

Friedenthal, Salm and others (52 and 53) used phosphate
mixtures, L. Michaelis (110) used phosphate and acetate
mixtures, as did also Henderson, Brode and W. Lange.
S0rensen also used glycocoU, citrate and borate mixtures.

The difficulty of using the colorimetric method for the
determination of the hydrogen-ion-concentration in gastric
juice is that the protein matter enters into combination with
various indicators and disturbs the investigation. In pepsin
investigations, therefore^ indicators of the azo group should be
used. On the other hand congo red cannot be used. Indicators
with the simplest composition are the best for the colorimetric
method e. g. p. nitrophenol and also the phtalein group. By
other experiments Sorensen proved that ali^arinsulphon acid
and lacmoid are useless as indicators when protein matter is
present. Tropaolin etc., (p. benzolsulphon acid azodiphenylamin
is bound by the acid albumen and cannot be used).
According to Sorensen and Falitsch we should use the following^
indicators with biological liquids.


Methyl violet Pr = 0.1 —



Mauvein « =0.1 —



Methyl orange « =3.1 —



Methyl red « = 4.2 —



Nitrophenol « = 5.0 —



Neutral red « = 6.8 —



Phenolphtalein « = 8.3 —


Between the two limits of Pr lie the limits which are of
use as indicators. According to Sorensen dimethylamidoazobenzol
lies between 2.9 and 4.0. In these experiments there was used
citrate mixtures and for purposes of accuracy there were intro-^
duced more mixtures than those given by Sorensen.

The standard solution used appears as follows:








ccm. citrate +

« « -}-

« « -|-

« * "i"

« « -["

« * ~h

« +

« « -f

c +

« +

« « -\-

« +

« 4-





9 •















« «


Ph =











































































As indicator there was used from 1 to 9 methyl violet (0.1
gramme dissolved in 1 litre of water, i.e.l per 1000, of which
1 ccm. was used).

From 7 to 15 dimethylamidoazobenzol (one drop of a 1 Voo
alcoholic solution). From 14 to 19 methyl red{().l grammes dis-
solved in 300 ccms absolute alcohol plus 200 ccms water, of
which 1 ccm. was used.) From 19 to 25 p. nitrophenol (0.4
grammes dissolved in 50 ccms absolute alcohol plus 940 ccms
water. (E. Merck, Darmstadt, of which 2 ccm. was used.) From

— 9 —

25 to 27 phenolphtalein (0.5 grammes dissolved in 500 ccms
alcohol plus 50 ccms water)

In the table given above: —

H.Cl = 0.1 n. hydrochloric acid.

NaOH = 0.1 n. caustic soda

Citrate zz 0.1 mol. solution
of secondary sodium citrate. This is made by dissolving 21.008
grammes crystallized citric acid in 200 ccms carbonate free n.
caustic soda thinned out with water to 1 litre.

Still better than the colorimetric method of determining
the hydrogen-ion-concentration is that recommended by L.
Michaelis (111) in 1917, electrometric titration designed for the
determination of the hydrogen-ion-concentration in gastric
juice. This Gaskette apparatus as it is called, however, is very
complicated, and therefore, as mentioned previously, at the con-
clusion of his recommendation he advises the use of dimethyl-
amidoazobenzol titration as a simpler and good method which
even if not quite exact gives the approximate hydrogen-ion-
concentration titrated in the manner which he further specifies.

Determination of the proteolytic capacity of the
gastric juice.

For a number of years I have occupied myself with the
determination of the proteolytic capacity of the gastric juice, and
in the course of these researches I have felt the want of a
simple and exact method. I have tried most of the commonest
methods such as BriicJce's method, Metfs method, Griltzners
method, Hammerschlag^ s method, Bettmann- Schroder's method.
Gross' method and Kohlenherger's pepsinometer. Of these Mett^s
and Hammerschlag's are the most commonly employed. Perhaps
Mett's is used most of all. As is known, is consists in the use
of thin glass tubes into which are sucked up the whites of hen's
eggs, which are heated to coagulation. These tiny tubes are
then placed in the gastric juice which is to be examined, and

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