Clinical Science (1972) 42, 2 3 ~ - 2 9 ~ .
MEDICAL RESEARCH SOCIETY
A meeting of the Medical Research Society was held at University College Hospital Medical
School, London, on Friday, 17 March 1972. The following Symposium was held and
Demonstrations and Communications presented.
membrane as an unstirred sheet, separating two weliDEMONSTRATIONS
1. A digital computer model for teaching and research mixed solutions.
2. In this wider sense, several types of membranes
in applied pulmonary physiology
are of biological importance. Examples are the ‘lipid
C. J. DICKINSON
(Department of Medicine)
based‘ cell membranes, basement membranes and the
2. Is sodium transport across colonic epithelium mainly ‘tight zeals’ or zonulae occludentes of epithelia.
extra-cellular?
3. Whereas both basement membranes and ‘tight
J. KERMODE,
D. PILLCHER
and C. J. EDMONDS seals’ show characteristics of penetration through
(Department of Clinical Research)
pores, other mechanisms, like carrier mediated trans3. Iodine metabolism in rats studied during a 6O-day port, etc., seem to be predominant in the lipid
intravenous infusion of ‘*’I
membranes.
I. V. B~~NAMSIRI
and B. D. THOMFWN(Department
4. The ‘tight seals’ may be very tight in some
of Clinical Research)
epithelia (frog skin, toad bladder, large intestine) but
they are highly leaky in others (gall bladder, proximal
4. A method for prolonged infusion of rat intestine
B. D. THOMPSON and C. J. EDMONDS
(Department tubule, small intestine).
5. Experiments in our laboratory and elsewhere
of Clinical Research)
5. Clinical measurement of the transepithelial electrical with frog skins, toad urinary bladder, etc., indicate
that the tightness of the ‘tight seals’ may be decreased
p.d. of human rectum and sigmoid colon
enormously (but reversibly) by an ‘outgoing’ osmotic
C. J. EDMONDS
(Department of Clinical Research)
gradient. The basis for this phenomenon and its
6. Preliminary studies in phenylalanine excretion
implications will be discussed in some detail.
C. W. I. OWENS
(Metabolic Unit)
I . Radwimmmassay of parathyroid hormone and B. FLUID AND ELECTROLYTE MOVEMENTS
selective venous catheterization in patients re-explored IN SMALL AND LARGE INTESTINE
for parathyroid twnours
D. R. DAW, D. R. IVES,
D. G. SHAW,B. M. THOMAS D. s. PARSONS
and L. C. A. WATSON
(Metabolic Unit)
Department of Biochemistry, University of Oxford
8. Measurement of red cell 2,3-diphospho-glycerate
Large quantities of electrolyte, principally sodium
E. NELSON
(Department of Clinical Haematology)
chloride, recirculate through the gastrointestinaltract.
9. Determination of oxygen affinity of whole blood Water absorption is secondary to a primary absorption of salt. Fluid secretion and fluid absorption differ
using the mixing technique and a micro method
M. CLUTTERBUCK
and A. J. BELLINGHAM
(Department only in the directionin which the net movement occurs.
Transepithelialsalt movements are believed to depend
of Clinical Haematology)
10. Morphological studies on transferrin uptake by cells upon the functioning of membrane systems organized
E. BAKER,T. C. APPLKKJN,C. F I S and
~ E. H. in the classical manner described by Ussing. There is
evidence that some, if not all, of the chloride is
MORQAN
(Department of Clinical Haematology)
absorbed by processes independent of the sodium,
11. Disseminated intravascular coagulation in the new- and that salt transport and carbon dioxidemetabolism
born
are interrelated. There are marked regional differences
R. RIVERS
(Departments of Clinical Haematology and in intestinal function. In many species the upper small
Paediatrics)
intestine is an organ in which salt is equilibrated; in
herbivorous animals it may be an area of secretion.
In the rat, dog and man bicarbonate is secreted into
SYMPOSIUM ON ION AND WATER MOVE the contents of the ileum and colon when sodium
MENTS THROUGH LIVING MEMBRANES
chloride solutions are absorbed. In the forestomach
of ruminants,and in the caecum and colon of herbiChairman and organizer: 0.M. WRONG
vorous animals and of other animals including man,
A. TRANSPORT OF WATER AND SOLUTES electrolytes, notably NH; and volatile fatty acids,
THROUGH LIVING MEMBRANES
are formed by microbial fermentation of exogenous
HANSH. USSINQ
and endogenous organic matter including ur&, and
Institute 0f Biological Chemktry, University Of absorbed, doubtla by specific transport processes,
Copenhagen,Denmark
although little is known about these. In the colon, in
1. Phenomenologically, it is advisable to de6ne a the presence of ammonium ions, bicarbonate is
I*
2 3 ~
2 4 ~
Medical Research Society
absorbed and not secreted. Stimulation or inhibition
of sodium transport systems asymmetrically arranged
in the membranes of absorbing epithelial cells might
induce secretion. Under the appropriate influence
absorbing cells may therefore become secreting cells.
Gastrointestinal hormones may be of significance in
fluid secretion in the intestine. Fluid secretion may
occur physiologically from the crypts of Lieberkiihn.
C. ELECTRICAL POTENTIAL DIFFERENCE
AND SODIUM TRANSPORT I N HUMAN
COLON AND RECTUM
and DIANAPILCHER
C. J. EDMONDS
M.R.C. Department of CIinical Research, University
College Hospital Medical School, London WC1E 6JJ
The mucosal epithelium of the colon and rectum is
electrically polarized, the blood side being positively
charged with respect to the lumen. When mineralocorticoid is given a considerable increase in the
electrical potential difference (p.d.) occurs, especially
in the distal part of the colon (Edmonds & Marriott,
1967, Journal of Endocrinology, 39, 517). We have
developed simple methods for measuring p.d. and
ionic fluxes across the epithelium of human rectum
and sigmoid colon and have investigated the relationship between p.d. and sodium transport. In the f i s t
series of experiments, the effect of altering the sodium
concentration in the lumen was investigated using
sulphate as the accompanying anion and maintaining
isotonicity by adding mannitol or magnesium sulphate. In normal subjects, p.d. decreased as the
sodium concentration was reduced and the change
was considerably exaggerated by aldosterone administration (an average change of 11 mV and 28 mV for a
sodium concentration change of 100 to 10 mEq/l, in
the normal and aldosterone treated individuals
respectively). Alterations in the concentration of
other cations had relatively little effect.
Measurement of the sodium unidirectional flux
rates across the epithelium showed that the lumen to
plasma flux was increased by mineralocorticoids
whereas plasma to lumen flux was little affected, and
p.d. change was correlated with the net sodium absorption. In most normal individuals flux rates were equal
(net flux zero) with luminal sodium concentrations of
2C30 mEq/l, but after rnineralocorticoids this value
was usually decreased to less than 10 mEq/l. Thus
aldosterone enables the mucosa to withdraw sodium
from the lumen against considerably increased electrical and chemical gradients. Water absorption also
occurs, apparently dependent on sodium absorption,
and with mineralocorticoid stimulation there is an
increase in the potassium plasma-to-lumen flux rate,
but this is probably only indirectly related to sodium
movements.
Our results indicate that the p.d. depends chiefly on
the active absorption of sodium, probably the consequence of the action of an electrogenic sodium pump.
The rectal epithelium is relatively accessible and
offers a useful means of study of ionic transport
systems in man.
D. THE RELATION BETWEEN FAECAL pH,
AMMONIA, AND BICARBONATE IN MAN
P. F. DOWN,L. AGOSTINI,
J. MURISON
and 0. M.
WRONG
Department of Medicine, University of Dundee
The colon is the major site of ammonia formation,
most of which is reabsorbed to reach the liver through
the portal circulation. Reabsorption of ammonia is
thought to be largely by passive non-ionic diffusion;
to investigate this possibility, ammonia, bicarbonate
and pH were measured in samples of faecal dialysate
from thirteen healthy subjects. Three subjects were
also studied while taking MgCOJ which increased
faecal pH, and Na2S04 which reduced faecal pH.
Faecal total ammonia concentrations and pH were
very variable, but showed a highly significant negative
correlation similar to that already established between
urinary ammonia and pH. Faecal bicarbonate concentrations were positively correlated with pH, and
calculated values for faecal Pco, were in the range
40-120 mmHg. Total ammonia concentrations were
negatively correlated with faecal bicarbonate.
These findings suggest that passive non-ionic
diffusion is the main mechanism by which ammonia
is absorbed by the colon, but do not exclude a minor
contribution from diffusion of ionized ammonium.
Colonic secretion of bicarbonate facilitates non-ionic
diffusion of ammonia by providing an anion which is
also absorbed by non-ionic diffusion, so maintaining
an alkaline faecal reaction which favours the formation of more un-ionized ammonia.
E. CARBONIC ANHYDRASE ISOENZYMES IN
THE GASTROINTESTINAL TRACT
M. J. CARTER
Department of Biochemistry, University of Oxford
Erythrocyte carbonic anhydrase occurs in two major
forms which are distinguished by their kinetic,
chemical, and certain physical properties. Thus one
type of enzyme (‘high activity’, HACA) has a specific
activity twenty times that of the other major type
(‘low activity’, LACA). Another consistent distinguishing feature of LACA, when compared with
HACA, is its high content of the amino acid serine.
Guinea-pig HACA occurs in large amounts in gastric,
colonic and caecal mucosae, with very little in the
small intestinal mucosa. LACA occurs only in the
colonic mucosa, and in especially high concentration,
in the caecal mucosa.
In considering the possible functions of CAs, the
question arises as to which physiological events in the
intestines seem best to correlate with these sharply