Table Of ContentADVANCES IN PHYSIOLOGICAL SCIENCES
Proceedings of the 28th International Congress of Physiological Sciences,
Budapest 1980
Volumes
1 — Regulatory Functions of the CNS. Principles of Motion and Organization
2 — Regulatory Functions of the CNS. Subsystems
3 — Physiology of Non-excitable Cells
4 — Physiology of Excitable Membranes
5 — Molecular and Cellular Aspects of Muscle Function
6 — Genetics, Structure and Function of Blood Cells
7 — Cardiovascular Physiology. Microcirculation and Capillary Exchange
8 — Cardiovascular Physiology. Heart, Peripheral Circulation and Methodology
9 — Cardiovascular Physiology. Neural Control Mechanisms
10 — Respiration
11 — Kidney and Body Fluids
12 — Nutrition, Digestion, Metabolism
13 — Endocrinology, Neuroendocrinology, Neuropeptides — I
14 — Endocrinology, Neuroendocrinology, Neuropeptides — II
15 — Reproduction and Development
16 — Sensory Functions
17 — Brain and Behaviour
18 — Environmental Physiology
19 — Gravitational Physiology
20 — Advances in Animal and Comparative Physiology
21 — History of Physiology
Satellite symposia of the 28th International Congress of Physiological Sciences
22 — Neurotransmitters in Invertebrates
23 — Neurobiology of Invertebrates
24 — Mechanism of Muscle Adaptation to Functional Requirements
25 — Oxygen Transport to Tissue
26 — Homeostasis in Injury and Shock
27 — Factors Influencing Adrenergic Mechanisms in the Heart
28 — Saliva and Salivation
29 — Gastrointestinal Defence Mechanisms
30 — Neural Communications and Control
31 — Sensory Physiology of Aquatic Lower Vertebrates
32 — Contributions to Thermal Physiology
33 — Recent Advances of Avian Endocrinology
34 — Mathematical and Computational Methods in Physiology
35 — Hormones, Lipoproteins and Atherosclerosis
36 — Cellular Analogues of Conditioning and Neural Plasticity
(Each volume is available separately.)
ADVANCES IN
PHYSIOLOGICAL SCIENCES
Satellite Symposium of the 28th International Congress of Physiological Sciences
Pecs, Hungary 1980
Volume 29
Gastrointestinal
Defence Mechanisms
Editors
Gy. Mozsik
Pecs, Hungary
O. Hanninen
Kuopio, Finland
T. Javor
Pecs, Hungary
PH
PERGAMON PRESS AKADEMIAI KIADO
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British Library Cataloguing in Publication Data
International Congress of Physiological Sciences,
Satellite Symposium (28th : 1980 : Pecs
Advances in physiological sciences.
Vol. 29 : Gastrointestinal defence mechanisms
1. Physiology — Congresses
I. Title II. Mozsik, Gy III. Hanninen, Ο
IV. Javor, Τ V. Gastrointestinal defence
mechanisms
591.1 QPI 80-41883
Pergamon Press ISBN 0 08 026407 7 (Series)
ISBN 0 08 027350 5 (Volume)
Akademiai Kiado ISBN 963 05 2691 3 (Series)
ISBN 963 05 2713 8 (Volume)
In order to make this volume available as economically and as
rapidly as possible the authors^ typescripts have been reproduced in
their original forms. This method unfortunately has its typographi-
cal limitations but it is hoped that they in no way distract the reader.
Printed in Hungary
1. Clara Sajgo (Budapest, Hungary) 2. E. Ezer (Budapest, Hungary) 3. Elisabeth Fay (Budapest ,
Hungary) 4. M. Kondo (Kyoto, Japan) 5. L. Csalay (Budapest, Hungary) 6. O. Hanninen (Kuopio,
Finland) 7. H. Autrup (Bethesda, USA) 8. M. Ahotupa (Turku, Finland) 9. M. Sajgo (Budapest,
Hungary) 10. Judith Matuz (Budapest, Hungary) 11. E. Hietanen (Turku, Finland) 12. J. Szolcsanyi
(Pecs, Hungary) 13. G. Csakvari (Budapest, Hungary) 14. A.-M. Saamanen (Kuopio, Finland) 15. M.
Outi (Kuopio, Finland) 16. Noemi Prajda (Budapest, Hungary) 17. Judith Kralovanszky (Budapest,
Hungary) 18. Gy. Mozsik (Pecs, Hungary) 19. Gy. Szabo (Budapest , Hungary) 20. A. Gad (Falun,
Sweden) 21. D. van der Waaij (Groningen, The Netherlands) 22. P. B. Morat (London, England) 23. B.
Simon (Heidelberg, FRG) 24. L. Nagy (Pecs, Hungary) 25. E. Heimsch (Ulm, FRG) 26. T. Javor (Pecs,
Hungary) 27. F. Varga (Pecs, Hungary) 28. S. M. Morrissay (London, England) 29. T. Bero (Pecs, Hun-
gary) 30. C. D. Klaassen (Kansas City, USA) 31. Kornelia Javor (Pecs, Hungary) 32. F. Tarnok (Pecs,
Hungary) 33. G. Tatar (Budapest, Hungary) 34. J. Szantay (Cluj-Napoca, Romania)
ν
PREFACE
The gastrointestinal tract has an important service function in the body.
It stores ingested food and beverages for digestion, prepares the various
components for absorption, transfers actively physiologically necessary com-
pounds into the blood stream and lympharoutes. On the other hand, the
gastrointestinal tract performs also excretory functions. Faeces form togeth-
er with the urine the two major means by which the body can get rid of the
solid and liquid vastes. Thus the gastrointestinal tract contributes in many
ways to the homeostasis in body. All these functions have gained a lot of
interest among scientists throughout the world, and many of these functions
have been clarified in details.
In addition to the various functions mentioned above the gastrointes-
tinal tract carries out also functions related to the defence of the body
against biological, chemical and physical agents. The gastrointestinal defence
mechanisms have not been for many years—in fact for decades—under a
separated detailed review.
Therefore the Finnish Physiological Society suggested to the Organizing
Committee of the 28th International Congress of Physiological Sciences
to hold the Gastrointestinal Defence Mechanisms as a topic of a satellite
symposium after the main congress. The suggestion was accepted and the
colleagues at the P6cs University Medical School were ready to take the local
responsibility for organizing the meeting.
The First International Symposium on the Gastrointestinal Defence
Mechanisms was held on July 20-22, 1980 in the University Medical School
of Pics, Hungary. Dr. Kaarlo Hartiala acted as the chairman of the Organiz-
ing Committee and Drs. Eino Hietanen, Osmo Hanninen, Tib or Jdvor and
Gyula Mozsik as members.
The aim of the symposium was to call together research workers study-
ing both the theoretical and practical aspects of the various gastrointestinal
defence mechanisms. This aim was reached as evidenced by the almost 40 pa-
pers presented during the symposium and found in the volume. Eleven of
them are more or less review type and others primary research reports. Thus,
although rather short period of time was available for the distribution of
message about the meeting, nearly all the topics could be included.
To help the readers, the papers of the volume have been divided into
eight sections carrying the subheadings: Circulation and Mucosal Defence,
xi
Defence and Secretory Functions, Resistance and Toxicity, Pefence by
Biotransformation and Nutrition, Immunomechanisms on Defence at Mucosa
and Second Line Defence at Liver and Enterohepatic Circulation. All the
sections contain few papers each.
The meeting showed that the research of the gastrointestinal defence
mechanisms requires an application of several methodologies and interdisci-
plinary approach. The conference brought together scientists with different
background, and we do hope that this book gets into the hands also of those
working in other fields and turns their interests to the gastrointestinal de-
fence mechanisms. The following years will show, if the exposure has been
fruitful and a Second International Symposium on the Gastrointestinal De-
fence Mechanisms convenes.
Pecs July 24th, 1980
Gyula MOZSIK,
Osmo HANNINEN
and
Tibor JAVOR
xii
WELCOMING ADDRESS
On the contrary to my long-term plans I have to make a last minute
cancellation due to health problems to attend the International Sympo-
sium on Gastrointestinal Defence Mechanisms. I personally expected much
of it as a stimulus of further work in this field which I myself had an
opportunity to enter about thirty years ago in the guidance of Dr. A. C. Ivy.
Dr. Ivy was an ideal rich and hard working scientist who contributed much
to various discoveries in the physiology and pathophysiology of the gastro-
intestinal tract. Dr. Ivy got me as well as many others infected by his
enthusiasm. His pupils in various parts of the world have provided much of
the knowledge we now have on the functions of the normal and disturbed
gastrointestinal tract.
Although the society has changed with it certain health problems even
related to the gastrointestinal tract, there is a lot to be done to solve the
basic mechanisms of the gastrointestinal defence in the gastrointestinal tract.
I myself have been interested in the biotransformation reactions and gly-
coproteins and can see so many questions still waiting for an answer. The
increasing use of various purposes means a big challenge for our gastrointes-
tinal tract and at the same time also a challenge to research workers trying to
clarify the defence mechanisms at this portal of entry.
The program of the First International Symposium on the Gastrointes-
tinal Defence Mechanisms has good coverage of the research work done in
many countries. Therefore I feel pity for being unable to participate.
With these lines I should like to thank with all my heart to the Hungarian
colleagues for seeing all the troubles of organizing the meeting and also the
Hungarian Academy of Sciences and its Publishing House (Akademiai Ki-
ado), Budapest—together with Pergamon Press, Oxford—for taking care of
the symposium proceedings.
Wishing all success to the meeting
in Turku on 9th July 1980
Kaarlo HARTIALA
xiii
Adv. Physiol Set. Vol. 29. Gastrointestinal Defence Mechanisms
Gy. Mozsik, 0. Hanninen, T. Javor (eds)
CIRCULATORY RESPONSES TO CHANGES
OF INTESTINAL CONTENTS
G. Szabo and I. Benyo
Traumatological Research Unit and Third Department of Surgery, Semmelweis University Medical
School, Budapest, Hungary
Metabolic and circulatory changes during digestion and ab-
sorption of food were analysed already by Brodie et al. in 1910.
Many studies have since confirmed that blood flow in the supe-
rior mesenteric vascular bed increases following a meal. This
postprandial mesenteric hyperaemia has been observed in man
/Brandt et al., 1955; Degenais et al. 1966/, conscious primate
/Vatner et al. 1974/, anaesthetized and conscious dogs /Burns
and Schenk, 1969; Fronek and Stahlgren, 1968; Varro et al.,
1967; Vatner et al. 1970/ and rats /Reininger and Sapirstein,
1957/. The blood flow through the superior mesenteric artery in
dogs starts to increase within 5 to 15 min following food in-
take, reaches a maximum in 30-90 and lasts for 3-7 h /Burns and
Schenk, 1969; Fronek and Stahlgren, 1968; Vatner et al. 1970/.
If food constituents are introduced directly into the duodenum
the circulatory reaction begins in less than 10 min /Chou et al
1976/.
The maximal increase in mesenteric blood flow is 150-200 %
but usually the augmentation is well below 100 %. This seems
to be a rather moderate increase because propranolol e.g. may
produce a much greater augmentation of flow /Lundgren 1967/.
There might be several reasons for the moderateness of this
prostprandial vasodilatation. In the above studies the blood
flow was measured to the gastrointestinal tract as a whole. It
seems unlikely, however, that maximal vasodilatation occurs si-
multaneously in ever part of it. The vasodilatation might be
localized to the mucosa with no or only moderate changes in the
perfusion of the muscular layer. It seems that intestinal moti-
lity as such does not increase significantly total intestinal
blood flow /Lundgren 1967/ and that the absorption of certain
foods may not induce any conspicious flow changes /Brand et al.
1955/. The composition of the ingested food and its degree of
digestion might be an important factor in the production of the
gastrointestinal flow response. Moreover, certain food consti-
tuents may increase the blood flow in some part of the gastro-
intestinal tract, but be without effect on the circulation of
other parts. Let us see a few examples for the above proposi-
tions .
3
While undigested food introduced into the duodenal or jeju-
nal lumen failed to increase venous outflow from the exteriori-
zed intestinal loop, digested food or its supernatant increased
it significantly by 13 % and 11 %, respectively /Chou et al.
1976, 1978/. In the jejunum bile alone had no effect, but intro-
duced in the ileal lumen it increased local blood flow and it
also markedly enhanced the hyperaemic effect of digested food
in the jejunum. Glucose solution increased the circulation of
the isolated jejunal loop in the dog /Varro et al. 1967/. The
intestinal hyperaemia is limited, however, only to the perfused
teritory /Van Heerder et al. 196 8/ and the increase of flow
occurs mainly in the mucosal layer /Yu and al. 1975/. Intraduo-
denal fat augmented flow in the cat superior mesenteric artery
by 50-100 % /Fara and al. 1969/. At physiological postprandial
concentrations in the jejunum micellar solutions of oleic acid
and monoolein increased flow, but 16 common dietary amino acids
did not. The hyperaemic effect of lipids required the presence
of taurocholate /Chou and al. 1978/.
The concentration of nutritients in the jejunal lumen must
exceed a certain value to produce local hyperaemia and, gener-
ally speaking, the greater the concentration of nutritients in
the chyme the greater the resultant hyperaemia. The differences
in circulatory effects are, however, not due to differences in
the osmolarity of the solutions since an unabsorbeable substan-
ce with the same osmotic concentration does not increase intes-
tinal blood flow /Kvietys and al. 1976/.
It seems, however, that the composition of the ingested
food is not the only factor leading to haemodynamic changes.
It was only recently realized that the cardiovascular system
responds to feeding in two distinctly different phases. During
presentation and ingestion of food cardiac output, heart rate
arterial pressure and vascular resistance in various vascular
beds are altered in a pattern similar to that observed at the
increase in sympathetic neural activity. Within 5-30 min, how-
ever cardiac output, heart rate, arterial pressure, the perfu-
sion of the kidney and of the myocardium return to control
levels, while mesenteric blood flow starts to rise. In humans
anticipated feeding increases also vagally mediated gastric
acid secretion /Moor and Motoki, 1979/. Pure psychic stimula-
tion may be as effective stimulant as feeding. The observations
suggest that in the first phase the anticipation and/or inges-
tion of food elicit a secretory and generalized cardiovascular
reaction, in the second phase i.e. during the digestion when
the ingested food reaches the intestines there is a circulatory
response confined to the digestive organs /Burns and Schenk,
1969; Fronek and Fronek, 1970; Vatner et al., 1970, 1974/. On
the other hand some textbooks state that there are nervous re-
ceptors in the walls of the duodenum stimulated by high concen-
tration of hydrogen ions and that the acidification of the duo-
denal contents leads even in absence of any food to marked
changes in gastrointestinal macro- and micromotility and secre-
tory activity. The automatic movements of the intestinal villi
are stimulated and their capillaries are dilated /Ludany et al.
1959/. The hepatic blood flow, measured with coupled thermo-
elements, hydrogen wash-out technique or BSP-clearance is sig-
nificantly increased /Benyo et al., 1965, 1966, 1974/.
4
In the studies about the effect of various nutritients on
gastrointestinal circulation usually only the superior mesente-
ric artery flow /SMAF/ has been measured. There are only a few
informations available concerning the effect of a meal on coe-
liac artery flow, which supplies the liver, stomach, duodenum
and pancreas. In order to gain information about the flow chan-
ges in the whole splanchnic vascular bed in the first series
of our experiments we have studied in dogs with non-cannulating
electromagnetic flow probes the effect of acidifying the duode-
nal contents on the blood flow in the hepatic artery and in the
portal vein.
In 13 mongrel dogs the ba-
sal blood flow in the hepatic
artery /HAF/ was 13.6 (SEM +
1.3) ml / min/100 g tissue weight
ml min1 100q in the portal vein /PVF/
20Ch 46.6 + 7.0 and total hepatic
blood flow /HBF/ was 53.5 +
teu 6.3 ml/min/kg. After the
AHFVPFHBF introduction of 3 ml/kg body
weight 0.1 Μ hydrochloric
acid into the duodenal lumen
HAF increased by 24.7 %, PVF
by 31.3 % and HBF by 29.2 %.
Maximum HAF change was attain-
ed in 2 to 7 min and the reac-
tion lasted 8 to 30 min. The
arterial and venous reaction:-
were usually not entirely
AHF VPFHBF synchronous. In the first mi-
nute after acid introduction
there was usually a drop in
arterial blood pressure, af-
ter which it returned to near-
ly control level. At the same
time there was a small increa-
se in portal venous pressure.
Hepatic artery inflow resis-
tance decreased by 11 %. The
most prominent change was the
32.5 % drop in mesenteric
arteriolar resistance. /Fig.1,2/
These experiments have
Fig. Effect of duodenal ins-
shown that the introduction
tTlIation of 0.1 and 0.5 Μ hyd-
of acid into the duodenum
rochloric acid on hepatic arte-
leads to a transitory increase
ry IAHFI, portal vein /VPF/ and
in mesenteric blood flow last-
total hepatic blood flow /HBF/
ing about 30 min. If it is
in anaesthetized dogs.
supposed that the flow reac-
F: blood flow, ml/min/100 g or-
tion is due to chemoreceptor
gan weight. White columns: be-
stimulation, it can be assumed
fore acid introduction; Shaded
that a stronger stimulus would
columns: after acid.
elicit a greater response and
that a prolonged stimulation
leads to a sustained flow
reaction. Actually in 5 dogs
5
